WO1995017209A1 - Vaccines - Google Patents
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- WO1995017209A1 WO1995017209A1 PCT/EP1994/004227 EP9404227W WO9517209A1 WO 1995017209 A1 WO1995017209 A1 WO 1995017209A1 EP 9404227 W EP9404227 W EP 9404227W WO 9517209 A1 WO9517209 A1 WO 9517209A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55572—Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55577—Saponins; Quil A; QS21; ISCOMS
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to novel vaccine formulations, to methods of their production and to their use in medicine.
- the present invention relates to an oil in water emulsion.
- Such emulsions comprise tocopherol, squalene, Tween 80, Span 85 and Lecithin and have useful adjuvant properties.
- Vaccines containing QS21, an Hplc purified non-toxic fraction derived from the bark of Quillaja Saponaria Molina, and/or 3 De-O-acylated monophosphoryl lipid A (3 D-MPL), together with such oil in water emulsions also form part of the invention.
- 3 De-O-acylated monophosphoryl lipid A is known from GB2220 211 (Ribi). Chemically it is a mixture of 3 De-O-acylated monophosphoryl lipid A with 4, 5 or 6 acylated chains and is manufactured by Ribi Immunochem Montana. A preferred form of 3 De-O-acylated monophosphoryl lipid A is disclosed in International Patent Application No. 92/116556.
- QS21 is a Hplc purified non toxic fraction of a saponin from the bark of the South American tree Quillaja Saponaria Molina and its method of its production is disclosed (as QA21) in US patent No. 5,057,540.
- Oil in water emulsions per se are known in the art, and have been suggested to be useful as adjuvant compositions (EPO 399843).
- the present invention is based on the surprising discovery that an oil in water emulsion of the present invention, which unlike emulsions of the prior art contain tocopherol, as such or in combination with QS21 and/or 3 D-MPL enhance immune responses to a given antigen. Such enhancement available affords better immunological responses than hitherto before.
- oil in water emulsions of the present invention when formulated with 3 D-MPL and QS21 are preferential stimulators of IgG2a production and TH1 cell response. This is advantageous, because of the known implication of THj response in cell mediated response. Indeed in mice induction of IgG2a is correlated with such an immune response.
- a vaccine formulation of the HTV antigen gpl20 in such a combination results in a powerful synergistic induction of gpl20 protein specific immune responses.
- the observation that it is possible to induce strong cytolytic T lymphocyte responses is significant as these responses, in certain animal models have been shown to induce protection against disease.
- the present inventors have shown that the combination of the adjuvants QS21 and 3D- MPL together with an oil in water emulsion with an antigen results in a powerful induction of CS protein specific CTL in the spleen.
- QS21 also enhances induction of CTL on its own, while 3D-MPL does not.
- Induction of CTL is easily seen when the target antigen is synthesised intracellularly (e.g. in infections by viruses, intracellular bacteria, or in tumours), because peptides generated by proteolytic breakdown of the antigen can enter the appropriate processing pathway, leading to presentation in association with class I molecules on the cell membrane.
- pre-formed soluble antigen does not reach this processing and presentation pathway, and does not elicit class I restricted CTL. Therefore conventional non-living vaccines, while eliciting antibody and T helper responses, do not generally induce CTL mediated Immunity.
- the combination of the two adjuvants QS21 and 3D-MPL together with an oil in water emulsion can overcome this serious limitation of vaccines based or recombinant proteins, and induce a wider spectrum of immune responses.
- CTL specific for CS protein have been shown to protect from malaria in mouse model systems (Romero et al. Nature 341 :323 (1989)). In human trials where volunteers were immunised using irradiated sporozoites of P. falciparum, and shown to be protected against subsequent malaria challenge, induction of CTL specific for CS epitopes was demonstrated (Malik et al. Proc. Natl. Acad. Sci. USA 88:3300 (1991)).
- the ability to induce CTL specific for an antigen administered as a recombinant molecules is relevant to malaria vaccine development, since the use of irradiated sporozoites would be impractical, on the grounds of production and the nature of the immune response.
- RTS is a hybrid protein comprising substantially all the C-terminal portion of the circumsporozoite (CS) protein of P.falciparum linked via four amino acids of the preS2 portion of Hepatitis B surface antigen to the surface (S) antigen of hepatitis B virus. It's full structure is disclosed in co-pending International Patent Application No. PCT EP92/02591, published under Number WO 93/10152 claiming priority from UK patent application No.9124390.7. When expressed in yeast RTS is produced as a lipoprotein particle, and when it is co-expressed with the S antigen from HBV it produces a mixed particle known as RTS,S.
- the ability to induce CTL responses would benefit vaccines against herpes simplex virus, cytomegalovirus, and generally all cases where the pathogen has an intracellular life stage.
- CTL specific for known tumour antigens could be induced by a combination of a recombinant tumour antigen and the two adjuvants. This would allow the development of anti cancer vaccines.
- the combination of 3D-MPL and QS21 together with an oil in water emulsion have been able to synergistically enhance interferon ⁇ production.
- the present inventors have demonstrated the potential of 3D-MPL and QS21 together with an oil in water emulsion by utilising a herpes simplex antigen known as gD2t.
- gD2t is a soluble truncated glycoprotein D from HS V-2 and is produced in CHO cells according to the methodology Berman et al. Science 222 524-527.
- IFN- ⁇ secretion is associated with protective responses against intracellular pathogens, including parasites, bacteria and viruses. Activation of macrophages by IFN- ⁇ enhances intracellular killing of microbes and increases expression of Fc receptors. Direct cytotoxicity may also occur, especially in synergism with lymphotoxin (another product of THl cells). IFN- ⁇ is also both an inducer and a product of NK cells, which are major innate effectors of protection. THl type responses, either through IFN- ⁇ or other mechanisms, provide preferential help for IgG2a immunoglobulin isotypes.
- Glycoprotein D is located on the viral envelope, and is also found in the cytoplasm of infected cells (Eisenberg R.J. et al J. of Virol. 1980 35 428-435). It comprises 393 amino acids including a signal peptide and has a molecular weight of approximately 60kD. Of all the HSV envelope glycoproteins this is probably the best characterized (Cohen et l. J. Virology 60 157-166). In vivo it is known to play a central role in viral attachment to cell membranes. Moreover, glycoprotein D has been shown to be able to elict neutralizing antibodies in vivo (Eing et al. J. Med Virology 127: 59-65). However, latent HSV2 virus can still be reactivated and induce recurrence of the disease despite the presence of high neutralizing antibodies titre in the patients sera. It is therefore apparent that the ability to induce neutralizing antibody alone is insufficient to adequately control the disease.
- any vaccine will need to stimulate not only neutralizing antibody, but also cellular immunity mediated through T-cells, particularly cytotoxic T-cells.
- the gU t is HSV2 glycoprotein D of 308 amino acids which comprises amino acids 1 though 306 of the naturally occurring glycoprotein with the addition of Asparagine and Glutamine at the C terminal end of the truncated protein.
- This form of the protein includes the signal peptide which is cleaved to yield a mature 283 amino acid protein.
- the production of such a protein in Chinese Hamster ovary cells has been described in Genentech's European patent EP-B-139 417.
- the mature truncated glycoprotein D (rgD2t) or equivalent proteins secreted from mammalian cells is preferably used in the vaccine formulations of the present invention.
- the formulations of the present invention are very effective in inducing protective immunity in a genital herpes model in guinea pigs. Even with very low doses of antigen (e.g. as low as 5 ⁇ g rgD2t) the formulations protect guinea pigs against primary infection and also stimulate specific neutralising antibody responses.
- the inventors, utilising formulation of the present invention have also demonstrated Effector cell mediated responses of the THl type in mice.
- a vaccine or pharmaceutical formulation comprising an antigen in conjunction with 3 De-O- acylated monophosphoryl lipid A, QS21and an oil in water emulsion wherein the oil in water emulsion comprises a metabolisible oil, such as squalene, alpha tocopherol and tween 80.
- a formulation is suitable for a broad range of monovalent or polyvalent vaccines.
- the oil in water emulsion may contain span 85.
- a preferred form of 3 De-O-acylated monophosphoyl lipio A is disclosed in International patent application published under No. 92116556 - SmithKline Beecham Biologicals s.a.
- the oil in water emulsion may be utilised on its own or with other adjuvants or immuno-stimulants and therefore an important embodiment of the invention is an oil in water formulation comprising squalene or another metabolisable oil, alpha tocopherol, and tween 80.
- the oil in water emulsion may also contain span 85 and/or Lecithin.
- the vaccine formulations will contain an antigen or antigenic composition capable of eliciting an immune response against a human or animal pathogen, which antigen or antigenic composition is derived from HIV-1, (such as gpl20 or gpl60), any of Feline Immunodeficiency virus, human or animal herpes viruses, such as gD or derivatives thereof or Immediate Early protein such as ICP27 from HSV1 or HSV2, cytomegalovirus ((esp Human)(such as gB or derivatives thereof), Varicella Zoster Virus (such as gpl, II or III), or from a hepatitis virus such as hepatitis B virus for example Hepatitis B Surface antigen or a derivative thereof, hepatitis A virus, hepatitis C virus and hepatitis E virus, or from other viral pathogens, such as Respiratory Syncytial virus, human papilloma virus or Influenza virus, or derived from bacterial pathogens such
- the formulations may also contain an anti-tumour antigen and be useful for immunotherapeutically treating cancers. .
- the formulation may also be useful for utilising with herpetic light particles such as described in International Patent Application No. PCT/GB92/00824 and, International Patent Application No. PCT/GB92/00179.
- the vaccine formulation of the invention comprises the HIV-1 antigen, gpl 20, especially when expressed in CHO cells.
- the vaccine formulation of the invention comprises gD2t as hereinabove defined.
- the ratio of QS21 : 3D-MPL will typically be in the order of 1 : 10 to 10 : 1; preferably 1 : 5 to 5 : 1 and often substantially 1 : 1.
- the preferred range for optimal synergy is 2.5: 1 to 1: 1 3D MPL: QS21.
- QS21 and 3D MPL will be present in a vaccine in the range 1 ⁇ g - 100 ⁇ g, preferably 10 ⁇ g - 50 ⁇ g per dose.
- the oil in water will comprise from 2 to 10% squalene, from 2 to 10% alpha tocopherol and from 0.3 to 3% tween 80.
- the ratio of squalene: alpha tocopherol is equal or less than 1 as this provides a more stable emulsion.
- Span 85 may also be present at a level of 1%. In some cases it may be advantageous that the vaccines of the present invention will further contain a stabiliser.
- Vaccine preparation is generally described in New Trends and Developments in Vaccines, edited by Voller et al., University Park Press, Baltimore, Maryland, U.S.A. 1978.
- Encapsulation within liposomes is described, for example, by Fullerton, U.S. Patent 4,235,877.
- Conjugation of proteins to macromolecules is disclosed, for example, by Likhite, U.S. Patent 4,372,945 and by Armor et al., U.S. Patent 4,474,757.
- each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccinees. Such amount will vary depending upon which specific immunogen is employed and how it is presented. Generally, it is expected that each dose will comprise 1-1000 ⁇ g of protein, preferably 2-100 ⁇ g, most preferably 4-40 ⁇ g. An optimal amount for a particular vaccine can be ascertained by standard studies involving observation of appropriate immune responses in subjects. Following an initial vaccination, subjects may receive one or several booster immunisation adequately spaced.
- the formulations of the present invention maybe used for both prophylatic and therapeutic purposes. Accordingly in one aspect, the invention provides a method of treatment comprising administering an effective amount of a vaccine of the present invention to a patient.
- Example 1 Vaccine formulation comprising the gpl 20 antigen of HTV-1.
- the two adjuvant formulations were made each comprising the following oil in water emulsion component.
- SB26 5% squalene 5% tocopherol 0.4% tween 80; the particle size was 500 nm size SB62: 5% Squalene 5% tocopherol 2.0% tween 80; the particle size was 180 nm
- Tween 80 is dissolved in phosphate buffered saline (PBS) to give a 2% solution in the PBS.
- PBS phosphate buffered saline
- 5g of DL alpha tocopherol and 5ml of squalene are vortexed to mix thoroughly.
- 90ml of PBS/Tween solution is added and mixed thoroughly.
- the resulting emulsion is then passed through a syringe and finally microfluidised by using an Ml 105 microfluidics machine.
- the resulting oil droplets have a size of approximately 180 nm.
- This emulsion was prepared in an analogous manner utilising 0.4% tween 80.
- mice were immunized subcutaneously at day 0 and 14. Each injection dose was administered in a lOO ⁇ l volume.
- gp 120 specific antibodies are essentially IgGl .
- the preferred combination is [SB26 + MPL + QS21] .
- Example 4 Screening of adjuvants for induction of protective anti lymphoma responses using idiotype as immunogen.
- mice Groups of 10 mice are injected (ip) with 10" " * tumor cells at day 0, and vaccinated with 100 ⁇ g of KLH- coupled immunoglobulin directed against BCL 1 epitoped (ratio of KLH/lg: 1/1), in different adjuvant formulations at days 3, 10, 20 (sc immunization in the back). Level of serum antibodies to KLH and to idiotype, as well as mouse death are monitored.
- Formulation 10 stands out as the most potent, both with respect to antibody titers, and with respect to survival (the only group with 100% survival).
- EXAMPLE 5 Various formulations of RTS,S
- RTS,S is described in International patent application no. WO93/10152 and was formulated for vaccination of Rheusus monkeys. Five animals were in each group:
- mice were inoculated and bled at 14 days post first immunisation and 12 days post second immunisation and tested for Anti hepatitis B surface antigen immunoglobulin. As can be seen from figure 1, animals receiving RTS,S, in SB60 had antibody titres almost six fold higher than any other group.
- the animals were inoculated and bled at 15 days post first immunisation and at day 7 and 15 post second immunisation and assayed for anti HBSAg antibody subtype.
- the emulsion SB62 when formulated with QS21 and 3D- MPL enhances preferentially and in a synergistic fashion the IgG2a antibody response while SB 62 alone or 3 D- MPL / QS21 induce a poor I gG2a response.
- OspA lipoprotein for B burgdorferi is described in European Patent Application 0418 827 Max Plank et al.
- mice Female Balb/c mice were immunized on day 0 and day 14 in the hind foot-pads with various formulations of NS1-ICP27. Each injection contained 5 ⁇ g ofNSl-ICP27 and combinations of SB26 oil-in- water emulsion, QS21 (10 ⁇ g) and MPL (25 ⁇ g).
- Popliteal lymphnode cells were obtained on day 28 and stimulated in vitro with syngeneic P815 cells transfected with the ICP27 gene. The cultures were then tested for specific cytolytic activity on P815 target cells transfected with ICP27 and P815 ICP27 negative controls. Specific lysis results at different effecto ⁇ target (E:T) ratios for different immunization groups were as follows:
- ICP 27 (5 ⁇ g) + MPL (25 ⁇ g) + QS21 (lO ⁇ g) + SB26
- ICP 27 (5 ⁇ g) + QS21 (10 ⁇ g) ICP 27 (5 ⁇ g) + SB26
- ICP 27 (5 ⁇ g) + MPL (25 ⁇ g) + QS21 (lO ⁇ g) ICP 27 (5 ⁇ g) + MPL (25 ⁇ g) + QS21 (lO ⁇ g) + SB26
- ICP 27 (5 ⁇ g) ICP 27 (5 ⁇ g) + MPL (25 ⁇ g) were negative.
- One dose contained 10 ⁇ g NS1-ICP27, 10 ⁇ g MPL and lO ⁇ g QS21.
- Two vaccinations were given at days 0 and 7.
- Mice were challenged at day 14 with 5.2 10 3 TCID50 of HSV2 strain MS. The appearance of zosteriform lesions and deaths were recorded until day 14 post challenge.
- ICP27 of HS V2 was expressed in E coli as a fusion protein with NS 1 fragment of influenza virus.
- the protective efficacy of the purified recombinant protein was evaluated in the murine zosteriform model, in combination with MPL QS21 formulations.
- Balb/c mice given two vaccinations with NS1-ICP27 combined either with MPL + QS21 or with an oil in water emulsion (SB26) + MPL and QS21 were completely protected against disease (no zosteriform lesions) and death following HSV2 wild type challenge. In contrast, protection was not observed in the mice vaccinated either with NS1-ICP27 alone or with NS1-ICP27 combined with SB26 without MPL and QS21.
- GROUPS IMMUNOGEN dose/FORMULATION ELISA TITERS (7 days PII) % IgGl %IgG2a % IgG2b
Abstract
The present invention provides vaccine compositions comprising an oil in water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccines' compositions are potent inducers of a range of immune responses.
Description
Vaccines
The present invention relates to novel vaccine formulations, to methods of their production and to their use in medicine. In particular, the present invention relates to an oil in water emulsion. Such emulsions comprise tocopherol, squalene, Tween 80, Span 85 and Lecithin and have useful adjuvant properties. Vaccines containing QS21, an Hplc purified non-toxic fraction derived from the bark of Quillaja Saponaria Molina, and/or 3 De-O-acylated monophosphoryl lipid A (3 D-MPL), together with such oil in water emulsions also form part of the invention.
3 De-O-acylated monophosphoryl lipid A is known from GB2220 211 (Ribi). Chemically it is a mixture of 3 De-O-acylated monophosphoryl lipid A with 4, 5 or 6 acylated chains and is manufactured by Ribi Immunochem Montana. A preferred form of 3 De-O-acylated monophosphoryl lipid A is disclosed in International Patent Application No. 92/116556.
QS21 is a Hplc purified non toxic fraction of a saponin from the bark of the South American tree Quillaja Saponaria Molina and its method of its production is disclosed (as QA21) in US patent No. 5,057,540.
Oil in water emulsions per se are known in the art, and have been suggested to be useful as adjuvant compositions (EPO 399843).
The present invention is based on the surprising discovery that an oil in water emulsion of the present invention, which unlike emulsions of the prior art contain tocopherol, as such or in combination with QS21 and/or 3 D-MPL enhance immune responses to a given antigen. Such enhancement available affords better immunological responses than hitherto before.
Additionally the oil in water emulsions of the present invention when formulated with 3 D-MPL and QS21 are preferential stimulators of IgG2a production and TH1 cell response. This is advantageous, because of the known implication of THj response in cell mediated response. Indeed in mice induction of IgG2a is correlated with such an immune response.
For example a vaccine formulation of the HTV antigen gpl20 in such a combination results in a powerful synergistic induction of gpl20 protein specific immune responses.
The observation that it is possible to induce strong cytolytic T lymphocyte responses is significant as these responses, in certain animal models have been shown to induce protection against disease.
The present inventors have shown that the combination of the adjuvants QS21 and 3D- MPL together with an oil in water emulsion with an antigen results in a powerful induction of CS protein specific CTL in the spleen. QS21 also enhances induction of CTL on its own, while 3D-MPL does not.
Induction of CTL is easily seen when the target antigen is synthesised intracellularly (e.g. in infections by viruses, intracellular bacteria, or in tumours), because peptides generated by proteolytic breakdown of the antigen can enter the appropriate processing pathway, leading to presentation in association with class I molecules on the cell membrane. However, in general, pre-formed soluble antigen does not reach this processing and presentation pathway, and does not elicit class I restricted CTL. Therefore conventional non-living vaccines, while eliciting antibody and T helper responses, do not generally induce CTL mediated Immunity. The combination of the two adjuvants QS21 and 3D-MPL together with an oil in water emulsion can overcome this serious limitation of vaccines based or recombinant proteins, and induce a wider spectrum of immune responses.
CTL specific for CS protein have been shown to protect from malaria in mouse model systems (Romero et al. Nature 341 :323 (1989)). In human trials where volunteers were immunised using irradiated sporozoites of P. falciparum, and shown to be protected against subsequent malaria challenge, induction of CTL specific for CS epitopes was demonstrated (Malik et al. Proc. Natl. Acad. Sci. USA 88:3300 (1991)).
The ability to induce CTL specific for an antigen administered as a recombinant molecules is relevant to malaria vaccine development, since the use of irradiated sporozoites would be impractical, on the grounds of production and the nature of the immune response.
RTS is a hybrid protein comprising substantially all the C-terminal portion of the circumsporozoite (CS) protein of P.falciparum linked via four amino acids of the preS2 portion of Hepatitis B surface antigen to the surface (S) antigen of hepatitis B virus. It's full structure is disclosed in co-pending International Patent Application No. PCT EP92/02591, published under Number WO 93/10152 claiming priority from UK
patent application No.9124390.7. When expressed in yeast RTS is produced as a lipoprotein particle, and when it is co-expressed with the S antigen from HBV it produces a mixed particle known as RTS,S.
In addition to human immunodeficiency virus and malaria vaccines, the ability to induce CTL responses would benefit vaccines against herpes simplex virus, cytomegalovirus, and generally all cases where the pathogen has an intracellular life stage.
Likewise, CTL specific for known tumour antigens could be induced by a combination of a recombinant tumour antigen and the two adjuvants. This would allow the development of anti cancer vaccines.
In certain systems, the combination of 3D-MPL and QS21 together with an oil in water emulsion have been able to synergistically enhance interferon γ production. The present inventors have demonstrated the potential of 3D-MPL and QS21 together with an oil in water emulsion by utilising a herpes simplex antigen known as gD2t. gD2t is a soluble truncated glycoprotein D from HS V-2 and is produced in CHO cells according to the methodology Berman et al. Science 222 524-527.
IFN-γ secretion is associated with protective responses against intracellular pathogens, including parasites, bacteria and viruses. Activation of macrophages by IFN-γ enhances intracellular killing of microbes and increases expression of Fc receptors. Direct cytotoxicity may also occur, especially in synergism with lymphotoxin (another product of THl cells). IFN-γ is also both an inducer and a product of NK cells, which are major innate effectors of protection. THl type responses, either through IFN-γ or other mechanisms, provide preferential help for IgG2a immunoglobulin isotypes.
Glycoprotein D is located on the viral envelope, and is also found in the cytoplasm of infected cells (Eisenberg R.J. et al J. of Virol. 1980 35 428-435). It comprises 393 amino acids including a signal peptide and has a molecular weight of approximately 60kD. Of all the HSV envelope glycoproteins this is probably the best characterized (Cohen et l. J. Virology 60 157-166). In vivo it is known to play a central role in viral attachment to cell membranes. Moreover, glycoprotein D has been shown to be able to elict neutralizing antibodies in vivo (Eing et al. J. Med Virology 127: 59-65). However, latent HSV2 virus can still be reactivated and induce recurrence of the disease despite the presence of high neutralizing antibodies titre in the patients sera. It
is therefore apparent that the ability to induce neutralizing antibody alone is insufficient to adequately control the disease.
In order to prevent recurrence of the disease, any vaccine will need to stimulate not only neutralizing antibody, but also cellular immunity mediated through T-cells, particularly cytotoxic T-cells.
In this instance the gU t is HSV2 glycoprotein D of 308 amino acids which comprises amino acids 1 though 306 of the naturally occurring glycoprotein with the addition of Asparagine and Glutamine at the C terminal end of the truncated protein. This form of the protein includes the signal peptide which is cleaved to yield a mature 283 amino acid protein. The production of such a protein in Chinese Hamster ovary cells has been described in Genentech's European patent EP-B-139 417.
The mature truncated glycoprotein D (rgD2t) or equivalent proteins secreted from mammalian cells, is preferably used in the vaccine formulations of the present invention.
The formulations of the present invention are very effective in inducing protective immunity in a genital herpes model in guinea pigs. Even with very low doses of antigen (e.g. as low as 5 μg rgD2t) the formulations protect guinea pigs against primary infection and also stimulate specific neutralising antibody responses. The inventors, utilising formulation of the present invention, have also demonstrated Effector cell mediated responses of the THl type in mice.
Accordingly, in one preferred embodiment of the present invention provides a vaccine or pharmaceutical formulation comprising an antigen in conjunction with 3 De-O- acylated monophosphoryl lipid A, QS21and an oil in water emulsion wherein the oil in water emulsion comprises a metabolisible oil, such as squalene, alpha tocopherol and tween 80. Such a formulation is suitable for a broad range of monovalent or polyvalent vaccines. Additionally the oil in water emulsion may contain span 85. A preferred form of 3 De-O-acylated monophosphoyl lipio A is disclosed in International patent application published under No. 92116556 - SmithKline Beecham Biologicals s.a.
The oil in water emulsion may be utilised on its own or with other adjuvants or immuno-stimulants and therefore an important embodiment of the invention is an oil in
water formulation comprising squalene or another metabolisable oil, alpha tocopherol, and tween 80. The oil in water emulsion may also contain span 85 and/or Lecithin.
Preferably the vaccine formulations will contain an antigen or antigenic composition capable of eliciting an immune response against a human or animal pathogen, which antigen or antigenic composition is derived from HIV-1, (such as gpl20 or gpl60), any of Feline Immunodeficiency virus, human or animal herpes viruses, such as gD or derivatives thereof or Immediate Early protein such as ICP27 from HSV1 or HSV2, cytomegalovirus ((esp Human)(such as gB or derivatives thereof), Varicella Zoster Virus (such as gpl, II or III), or from a hepatitis virus such as hepatitis B virus for example Hepatitis B Surface antigen or a derivative thereof, hepatitis A virus, hepatitis C virus and hepatitis E virus, or from other viral pathogens, such as Respiratory Syncytial virus, human papilloma virus or Influenza virus, or derived from bacterial pathogens such as Salmonella, Neisseria, Borrelia (for example OspA or OspB or derivatives thereof), or Chlamydia, or Bordetella for example P.69, PT and FHA, or derived from parasites such as plasmodium or Toxoplasma.
The formulations may also contain an anti-tumour antigen and be useful for immunotherapeutically treating cancers. .
In an immunotherapeutic animal model for B cell lymphoma, where BCL-1 mouse lymphoma cells are adminstered intaperitonelly to Balb/c mice on day 0, and mice are vaccinated on days 3, 10 and 20 with the BCL-1 Idlotype, formulation SB62/MPL/QS21 stands out as the most potent, both with respect to antibody titers, and with respect to survival (the only group with 100% survival). Similarly the ability of this formulation to stimulate cytotoxic T lymphocytes to the antigens included make them a good candidate for formulation of cancer antigens (eg melanoma antigens MAGE-1 and MAGE-3 for immunotherapy of tumors by active vaccination).
The formulation may also be useful for utilising with herpetic light particles such as described in International Patent Application No. PCT/GB92/00824 and, International Patent Application No. PCT/GB92/00179.
Derivatives of Hepatitis B Surface antigen are well known in the art and include, inter alia, those PreSj, PreS2 S antigens set forth described in European Patent applications EP-A-414 374; EP-A-0304 578, and EP 198-474. In one preferred aspect the vaccine formulation of the invention comprises the HIV-1 antigen, gpl 20, especially when
expressed in CHO cells. In a further embodiment, the vaccine formulation of the invention comprises gD2t as hereinabove defined.
In a further aspect of the present invention there is provided a vaccine as herein described for use in medicine.
The ratio of QS21 : 3D-MPL will typically be in the order of 1 : 10 to 10 : 1; preferably 1 : 5 to 5 : 1 and often substantially 1 : 1. The preferred range for optimal synergy is 2.5: 1 to 1: 1 3D MPL: QS21. Typically for human administration QS21 and 3D MPL will be present in a vaccine in the range 1 μg - 100 μg, preferably 10 μg - 50 μg per dose. Typically the oil in water will comprise from 2 to 10% squalene, from 2 to 10% alpha tocopherol and from 0.3 to 3% tween 80. Preferably the ratio of squalene: alpha tocopherol is equal or less than 1 as this provides a more stable emulsion. Span 85 may also be present at a level of 1%. In some cases it may be advantageous that the vaccines of the present invention will further contain a stabiliser.
Vaccine preparation is generally described in New Trends and Developments in Vaccines, edited by Voller et al., University Park Press, Baltimore, Maryland, U.S.A. 1978. Encapsulation within liposomes is described, for example, by Fullerton, U.S. Patent 4,235,877. Conjugation of proteins to macromolecules is disclosed, for example, by Likhite, U.S. Patent 4,372,945 and by Armor et al., U.S. Patent 4,474,757.
The amount of protein in each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccinees. Such amount will vary depending upon which specific immunogen is employed and how it is presented. Generally, it is expected that each dose will comprise 1-1000 μg of protein, preferably 2-100 μg, most preferably 4-40 μg. An optimal amount for a particular vaccine can be ascertained by standard studies involving observation of appropriate immune responses in subjects. Following an initial vaccination, subjects may receive one or several booster immunisation adequately spaced.
The formulations of the present invention maybe used for both prophylatic and therapeutic purposes.
Accordingly in one aspect, the invention provides a method of treatment comprising administering an effective amount of a vaccine of the present invention to a patient.
The following examples illustrate the invention.
Examples
Example 1 Vaccine formulation comprising the gpl 20 antigen of HTV-1.
The two adjuvant formulations were made each comprising the following oil in water emulsion component.
SB26: 5% squalene 5% tocopherol 0.4% tween 80; the particle size was 500 nm size SB62: 5% Squalene 5% tocopherol 2.0% tween 80; the particle size was 180 nm
1(a) Preparation of emulsion SB62 (2 fold concentrate)
Tween 80 is dissolved in phosphate buffered saline (PBS) to give a 2% solution in the PBS. To provide 100 ml two fold concentrate emulsion 5g of DL alpha tocopherol and 5ml of squalene are vortexed to mix thoroughly. 90ml of PBS/Tween solution is added and mixed thoroughly. The resulting emulsion is then passed through a syringe and finally microfluidised by using an Ml 105 microfluidics machine. The resulting oil droplets have a size of approximately 180 nm.
1(b) Preparation of emulsion SB26
This emulsion was prepared in an analogous manner utilising 0.4% tween 80.
1(c) Other emulsions as depicted in Table 1 were made in an analogous manner. These are tested in the experiments as detailed in the following examples.
1(d) Preparation of gp 120 QS21/3D MPL oil in water formulation.
To the emulsion of 1 a) or b) or c) an equal volume of twice concentrated rgpl20 (either 20μg or lOOμg) was added and mixed. This was combined with 50μg/ml of 3D-MPL and 20μg/ml of QS21 to give the final formulation. Buffer was sed according to salt content and pH.
Table 3 shows the effectiveness of SB26, utilising gpl20 from HIV and 50μg/ml 3D MPL (MPL) and 20μg/ml of QS21. The results show the geometric mean titre (GMT) after the second (PI 1) and third (Pi l l) inoculations as well as cell mediated responses (CMI) to lymphocyte prolipheration and γ interferon production.
Example 2
Introduction: Evaluation of an HIV gp 120 emulsion system
In this experiment, four emulsions are compared [SB26, SB 62, SB40, SB61]. The influence of each formulation's component (antigen, emulsion, 3D- MPL, QS21) is evaluated.
2(b) Groups of animals utilised
There are 22 groups of 5 animals each group received a different vaccine formulation.
- gr 1 -4 : gp 120 ( 1 Oμg) / no emuls ± [3D-MPL, QS21 ]
- gr 5-9: gp 120 (lOμg) / SB26 ± [3D-MPL, QS21] - gr 10: no antigen / SB26 + [3D-MPL, QS21]
- gr 11-12: gp 120 (lOμg) / SB62 ± [3D-MPL, QS21]
- gr 13-16: gp 120 (lOμg) / SB40 ± [3D-MPL, QS21]
- gr 17-20. gp 120 (lOμg) / SB61 ± [3D-MPL, QS21]
- gr 21-22: gp 120 (5μg) / SB26 ± [3D-MPL, QS21]
- Assays: - antibody titers to gp 120W61D and isotype analysis (all groups)
2(c) Immunization and bleeding schedule
- animals were immunized with gp 120W61D, formulated in different o/w emulsions in the presence of 5μg 3D-MPL and 5μg QS21 per dose. Negative controls received the equivalent formulations without any antigen.
animals were immunized subcutaneously at day 0 and 14. Each injection dose was administered in a lOOμl volume.
blood samples were obtained before Immunization (day 0) and after Immunization on days 14 (post I), 21 and 28 (7 and 14d. post II).
2(d) Analysis of the serological response:
the 14 days post I and post II serological response was evaluated in a direct ELISA assay to gp 120W61D.
the 14 days post II response was also characterized regarding the isotypes of gp 120W61D specific antibodies induced in mice after immunization.
3 RESULTS AND DISCUSSION:
The results are depicted on Table 2
a) Comparison of emulsions in the presence or absence of 3D-MPL/QS21 :
Addition of emulsions SB26, SB40 or SB62 to the antigen induces higher antibody titers; In the absence of immunostimulants, the gp 120 specific antibodies are essentially IgGl .
- Addition of immunostimulants 3D-MPL and QS21 induces a huge serological response and a shift of antibodies from IgGl type to IgG2a IgG2b: This correlated with cell mediated immunity.
The preferred combination is [SB26 + MPL + QS21] .
c) gpl20/SB26 formulation:
No significant difference in serological response is observed between group 8 and group 9:. addition of the gp 120 before or after the other components of the formulation.
d) Antigen dose:
Both 5 and 10 μg of gp 120 formulated in SB26 induce high serological response (groups 5-8 and 21-22) .
Example 3 HSV rgU2t formulation
In analogous manner to that set forth in Example la) formulation comprising the herpes simplex antigen rgD2t was made and used to vaccinate guinea pigs. Such
formulation induced protection against both recurrent and initial disease in the guinea pig model.
Example 4 Screening of adjuvants for induction of protective anti lymphoma responses using idiotype as immunogen.
Therapeutic vaccination of Balb/c mice with idiotype from BCL1 lymphoma cells.
A review of the BALB/C B-cell lymphoma model is discussed by Yefenoh et al. Current opinions Immunobiology 1993 5:740-744.
Groups of 10 mice are injected (ip) with 10""* tumor cells at day 0, and vaccinated with 100 μg of KLH- coupled immunoglobulin directed against BCL 1 epitoped (ratio of KLH/lg: 1/1), in different adjuvant formulations at days 3, 10, 20 (sc immunization in the back). Level of serum antibodies to KLH and to idiotype, as well as mouse death are monitored.
Formulations tested: group# adjuvant MPL: lOμg
1 none (no antigen) QS21 : lOμg
2 none
3 Freund
4 Alum
5 Alum/MPL
6 Alum/MPL/QS21
7 QS21
8 MPL/QS21
9 SB62MPL
10 SB62/MPL/QS21
groups 12-15: different adjuvants without antigen
Formulations 8, 9, 10, behaved consisently better as compared to the others. Formulation 10 stands out as the most potent, both with respect to antibody titers, and with respect to survival (the only group with 100% survival).
EXAMPLE 5 Various formulations of RTS,S
a) Evaluated in monkeys
RTS,S is described in International patent application no. WO93/10152 and was formulated for vaccination of Rheusus monkeys. Five animals were in each group:
Group I RTS,S, 3D-MPL(50μ), AL(OH)3 Group II RTS,S, QS21(20μ), AL(OH)3
Group III RTS,S, 3D-MPL(50μ), QS21(20μ)
Group IV RTS,S, 3D-MPL(50μ), QS21 AL(OH)3
Group V RTS,S, 3D-MPL(10μ), QS21 AL(OH)3
Group VI RTS,S, 3D-MPL(50μ), QS21 SB60
The animals were inoculated and bled at 14 days post first immunisation and 12 days post second immunisation and tested for Anti hepatitis B surface antigen immunoglobulin. As can be seen from figure 1, animals receiving RTS,S, in SB60 had antibody titres almost six fold higher than any other group.
b) Various formulations of RTS,S - Evaluated in mice
7 groups of animals received the following formulations
Group 1 RTS,S SB62
Group 2 RTS,S QS21 3D-MPL
Group 3 RTS,S QS21 3D-MPL SB26
Group 4 RTS,S 3D-MPL A1(0H)3
Group 5 RTS,S A1(0H)3
Group 6 Plain
Group 7 Negative control
(RTS,S - 5μg/dose, 3 D-MPL 5μg/dose QS21 5μg/dose)
The animals were inoculated and bled at 15 days post first immunisation and at day 7 and 15 post second immunisation and assayed for anti HBSAg antibody subtype. As can be seen from figure 2, the emulsion SB62 when formulated with QS21 and 3D-
MPL enhances preferentially and in a synergistic fashion the IgG2a antibody response while SB 62 alone or 3 D- MPL / QS21 induce a poor I gG2a response.
EXAMPLE 6: Evaluation of different B burgdorferi OspA formulations
6.1 Evaluation of different formulations of B burgdorferi ZS7 Osp A lipoproteins.
OspA lipoprotein for B burgdorferi is described in European Patent Application 0418 827 Max Plank et al.
The following formulations were tested in balb/c mice
1. OspA + Al(OH)3
2. OspA + Al(OH)3 + 3D-MPL (lOμ) 3. OspA + Al(OH)3 + 3D-MPL (30μ)
4. OspA + Al(OH)3 + 3D-MPL (lOμ) + QS21 (5μ)
_. 5. OspA + Al(OH)3 + 3D-MPL (30μ) + QS21 (15μ)
6. OspA + SB60 + 3D-MPL (lOμ) + QS21 (5μ)
7. OspA + SB60 + 3D-MPL (30μ) + QS21 (15μ)
and antibody titres and sub types studied seven days following a first inoculation and seven days post second inoculation (inoculations were at day 0, and 14).
The results depicted graphically in figures 3 and 4 and show that the formulations of the present invention induce high levels of antibodies and these are preferentially of the IgG2a subtype.
EXAMPLE 7:
a) HSV-2 ICP 27
Female Balb/c mice were immunized on day 0 and day 14 in the hind foot-pads with various formulations of NS1-ICP27. Each injection contained 5 μg ofNSl-ICP27 and combinations of SB26 oil-in- water emulsion, QS21 (10 μg) and MPL (25 μg).
Popliteal lymphnode cells were obtained on day 28 and stimulated in vitro with syngeneic P815 cells transfected with the ICP27 gene. The cultures were then tested for specific cytolytic activity on P815 target cells transfected with ICP27 and P815 ICP27 negative controls.
Specific lysis results at different effectoπtarget (E:T) ratios for different immunization groups were as follows:
ICP 27 (5μ g)
E:T P815 P815 transfected with ICP 27 clone 121
100:1 -1 0
30:1 -2 -3
10:1 3 0
3:1 1 0
1:1 2 2
0.3:1 2 2
ICP27(5μg) + MPL(25μg)
E:T P815 P815 transfected with ICP 27 clone 121
100:1 5 7
30:1 2 2
10:1 1 2
3:1 -1 -1
1:1 -2 -2
0.3:1 -4 -1
ICP27(5μg) + QS21(10μg)
E:T P815 P815 transfected with ICP 27 clone 121
100:1 4 17
30:1 5 10
10:1 3 7
3:1 4 5
1:1 3 5
0.3:1 0 1
ICP 27 (5μg) + SB26
E:T P815 P815 transfected with ICP 27 clone 121
100:1 5 20
30:1 1 19
10:1 2 12
3:1 -2 7
1:1 1 5
0.3:1 1 2
ICP 27 (5μg) + MPL (25 μg) + QS21 (lOμg)
E:T P815 P815 transfected with ICP 27 clone 121
100: 1 4 13
30:1 5 12
10: 1 4 17
3: 1 1 3
1 :1 0 3
0.3:1 -1 -2
ICP 27 (5μg) + MPL (25 μg) + QS21 (lOμg) + SB26
E:T P815 P815 transfectes avec ICP27 clone 121
100: 1 2 20
30: 1 0 17
10:1 3 19
3: 1 3 8
1 : 1 1 6
0.3: 1 2 3
Low ICP27 specific % lysis was obtained in immunization groups:
ICP 27 (5μg) + QS21 (10μg) ICP 27 (5μg) + SB26
ICP 27 (5μg) + MPL (25 μg) + QS21 (lOμg) ICP 27 (5μg) + MPL (25 μg) + QS21 (lOμg) + SB26
while
ICP 27 (5μg) ICP 27 (5μg) + MPL (25μg) were negative.
Thus these data show induction of CTL by recombinant NS1-ICP27 in oil-in- water emulsion alone or with QS21 and MPL; or with QS21.
b) Groups of 5 Balb/c mice were vaccinated in the footpad with the different vaccines (NS1-1CP27/NS1-ICP27 MPL + QS21/NS1-ICP27 SB26 = MPL and QS21/ adjuvant alone). One dose contained 10 μg NS1-ICP27, 10 μg MPL and lOμg QS21.
Two vaccinations were given at days 0 and 7. Mice were challenged at day 14 with 5.2 103 TCID50 of HSV2 strain MS. The appearance of zosteriform lesions and deaths were recorded until day 14 post challenge.
ICP27 of HS V2 was expressed in E coli as a fusion protein with NS 1 fragment of influenza virus. The protective efficacy of the purified recombinant protein was evaluated in the murine zosteriform model, in combination with MPL QS21 formulations. Balb/c mice given two vaccinations with NS1-ICP27 combined either with MPL + QS21 or with an oil in water emulsion (SB26) + MPL and QS21 were completely protected against disease (no zosteriform lesions) and death following HSV2 wild type challenge. In contrast, protection was not observed in the mice vaccinated either with NS1-ICP27 alone or with NS1-ICP27 combined with SB26 without MPL and QS21.
Table 1 Vehicles two fold concentrated
Table 2 HIV gp 120W61D / MOUSE IMMUNOGENICITY (94243) / BALB / C (F.P.)
GROUPS IMMUNOGEN (dose)/FORMULATION ELISA TITERS (7 days PII) % IgGl %IgG2a % IgG2b
1 gP120 lOμg 494 100 0 0
2 gP120 lOμg + 3D-MPL 5μg 4164 54 15 32
3 gP120 10μg + QS21 5μg 21515 89 4 8
4 gP120 lOμg + 3D-MPL + QS21 52749 22 60 18
5 gP120 10μg / SB26 12205 94 2 4
6 gP120 lOμg / SB26 + 3D-MPL 87388 31 42 27
7 gP120 10μg / SB26 + QS21 51020 73 15 13
8 gP120 lOμg / SB26 + 3D-MPL + QS21 178169 23 57 21
9 SB26 + 3D-MPL + QS21 / gP120 lOμg 185704 22 60 19
11 gP120 10μg / SB62 10348 92 8 0 I
12 gP120 lOμg / SB62 + 3D-MPL + QS21 21739 54 37 9 _________
13 gP120 10μg / SB40 36320 90 7 4
14 gP120 lOμg / SB40 + 3D-MPL 285219 31 44 25
15 gP120 10μg / SB40 + QS21 48953 78 15 7
16 gP120 lOμg / SB40 + 3D-MPL + QS21 209217 14 67 18
17 gP120 10μg / SB61 <50 - - _
18 gP120 lOμg / SB61 + 3D-MPL 77515 31 50 19
19 gP120 10μg / SB61 + QS21 40737 74 13 13
20 gP120 lOμg / SB61 + 3D-MPL + QS21 59673 29 57 14
21 gP120 5μg / SB26 25089 99 0 1
22 gP120 5μg / SB26 + 3D-MPL + QS21 242736 18 61 21
ELISA titers to gp 120 W61D: geomean of 5 individual titers, calculated by LINEST
Table 3 3D-MPL based rormiilations: HIV project IVIonkcv studies
Claims
1. A vaccine composition comprising an antigen and/or antigenic composition, QS21, 3 De-O-acylated monophosphoryl lipid A (3D-MPL) and an oil in water emulsion wherein the oil in water emulsion has the following composition: a metabolisible oil, such as squalene, alpha tocopherol and tween 80.
2. A vaccine as claimed in claim 1 wherein the ratio of QS21 :3D-MPL is from 1:10 to 10:1.
3. A vaccine composition as claimed in claim 1 or 2 capable of invoking a cytolytic T cell response in a mammal to the antigen or antigenic composition.
4. A vaccine composition as claimed in any of claims 1 to 3 capable of stimulating interferon γ production.
5. A vaccine composition as claimed in any of claims 1 to 4 wherein the ratio of QS21:3D-MPL is from 1:1 to 1:2.5.
6. A vaccine composition as claimed herein comprising an antigen or antigenic composition derived from any of Human Immunodeficiency Virus, Feline Immunodeficiency Virus, Herpes Simplex Virus type 1, Herpes Simplex virus type 2, Human cytomegalovirus, Hepatitis AB,C or E, Respiratory Syncytial virus, human papilloma virus, Influenza virus, Salmonella, Neisseria, Borrelia, Chlamydia, Bordetella, Plasmodium or Toxoplasma.
7. A vaccine as claimed in any of claim 1 to 5 wherein the antigen is a tumour antigen.
8. Use of composition as defined in any of claims 1 to 5 for the manufacture of a vaccine for the prophylatic treatment of viral, bacterial, or parasitic infections.
9. Use of composition as defined in any of claims 1 to 5 for the manufacture of a vaccine for the immunotherapeutic treatment of viral, bacterial, parasitic infections or cancer.
10. A method of treating a mammal suffering from or susceptible to a pathogenic infection comprising the administration of a safe and effective amount of a composition according to any of claims 1 to 5.
11. A method of treating a mammal suffering from cancer comprising the administration of a safe and effective amount of a composition according to any of claims 1 to 5.
12. A process for making a vaccine composition according to claims 1 to 5 comprising admixing QS21, 3D-MPL and the oil in water emulsion as defined in claim 1 with an antigen or antigenic composition.
13. A vaccine composition comprising an antigen or antigenic composition in association with an oil in water emulsion which emulsion comprises: a metabolisable oil , alpha tocopherol, and tween 80.
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DK03075344T DK1327451T3 (en) | 1993-12-23 | 1994-12-20 | Adjuvants based on an emulsion and MPL for vaccines |
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GB939326253A GB9326253D0 (en) | 1993-12-23 | 1993-12-23 | Vaccines |
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US9463198B2 (en) | 2013-06-04 | 2016-10-11 | Infectious Disease Research Institute | Compositions and methods for reducing or preventing metastasis |
WO2017200852A1 (en) | 2016-05-16 | 2017-11-23 | Infectious Disease Research Institute | Formulation containing tlr agonist and methods of use |
EP3251680A1 (en) | 2008-05-22 | 2017-12-06 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
WO2017210364A1 (en) | 2016-06-01 | 2017-12-07 | Infectious Disease Research Institute | Nanoalum particles containing a sizing agent |
US9895435B2 (en) | 2012-05-16 | 2018-02-20 | Immune Design Corp. | Vaccines for HSV-2 |
US10039823B2 (en) | 2005-12-13 | 2018-08-07 | Glaxosmithkline Biologicals, S.A. | Vaccine compositions comprising a saponin adjuvant |
US10149901B2 (en) | 2009-02-10 | 2018-12-11 | Seqirus UK Limited | Influenza vaccines with reduced amounts of squalene |
WO2019051149A1 (en) | 2017-09-08 | 2019-03-14 | Infectious Disease Research Institute | Liposomal formulations comprising saponin and methods of use |
US10842867B2 (en) | 2005-11-04 | 2020-11-24 | Seqirus UK Limited | Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture |
US11236366B2 (en) | 2008-08-28 | 2022-02-01 | Novartis Ag | Production of squalene from hyper-producing yeasts |
US11707520B2 (en) | 2005-11-03 | 2023-07-25 | Seqirus UK Limited | Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture |
Families Citing this family (510)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1463097A (en) | 1996-01-04 | 1997-08-01 | Rican Limited | Helicobacter pylori bacterioferritin |
US7517952B1 (en) * | 1997-02-25 | 2009-04-14 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
US20030185830A1 (en) * | 1997-02-25 | 2003-10-02 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
US20060024301A1 (en) * | 1997-02-25 | 2006-02-02 | Corixa Corporation | Prostate-specific polypeptides and fusion polypeptides thereof |
GB9711990D0 (en) * | 1997-06-11 | 1997-08-06 | Smithkline Beecham Biolog | Vaccine |
AU734180B2 (en) * | 1997-08-29 | 2001-06-07 | Antigenics Llc | Compositions comprising the adjuvant qs-21 and polysorbate or cyclodextrin as excipient |
GB9718901D0 (en) * | 1997-09-05 | 1997-11-12 | Smithkline Beecham Biolog | Vaccine |
GB9724531D0 (en) | 1997-11-19 | 1998-01-21 | Smithkline Biolog | Novel compounds |
US6913745B1 (en) | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US6923964B1 (en) | 1997-12-02 | 2005-08-02 | Neuralab Limited | Active immunization of AScr for prion disorders |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
US6905686B1 (en) | 1997-12-02 | 2005-06-14 | Neuralab Limited | Active immunization for treatment of alzheimer's disease |
US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US6710226B1 (en) | 1997-12-02 | 2004-03-23 | Neuralab Limited | Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics |
US6761888B1 (en) | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
JP4768121B2 (en) | 1998-02-05 | 2011-09-07 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | Tumor associated antigens from the MAGE family and the nucleic acid sequences encoding them, the use of fusion proteins and for the preparation of compositions for vaccination |
US20020147143A1 (en) | 1998-03-18 | 2002-10-10 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
AU753995B2 (en) | 1998-04-07 | 2002-10-31 | Corixa Corporation | Fusion proteins of mycobacterium tuberculosis antigens and their uses |
BR9910269A (en) * | 1998-05-07 | 2001-01-09 | Corixa Corp | Adjuvant composition and methods for its use |
US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
EP1102790B1 (en) | 1998-08-07 | 2014-05-07 | University of Washington | Immunological Herpes Simplex Virus antigens and methods for use thereof |
US20030235557A1 (en) | 1998-09-30 | 2003-12-25 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
CN100365120C (en) | 1998-12-08 | 2008-01-30 | 科里克萨有限公司 | Compounds and methods for treatment and diagnosis of chlamydial infection |
US20020119158A1 (en) | 1998-12-17 | 2002-08-29 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
US6579973B1 (en) | 1998-12-28 | 2003-06-17 | Corixa Corporation | Compositions for the treatment and diagnosis of breast cancer and methods for their use |
US7198920B1 (en) | 1999-01-29 | 2007-04-03 | Corika Corporation | HER-2/neu fusion proteins |
US6835721B2 (en) * | 1999-02-01 | 2004-12-28 | Eisai Co., Ltd. | Immunomodulatory compounds and methods of use thereof |
DE60011571T2 (en) * | 1999-02-01 | 2005-08-18 | Eisai Co., Ltd. | COMPOUNDS WITH IMMUNOLOGICAL ADJUVANT EFFECT |
US6551600B2 (en) | 1999-02-01 | 2003-04-22 | Eisai Co., Ltd. | Immunological adjuvant compounds compositions and methods of use thereof |
US20040006242A1 (en) | 1999-02-01 | 2004-01-08 | Hawkins Lynn D. | Immunomodulatory compounds and method of use thereof |
US7915238B2 (en) * | 1999-02-01 | 2011-03-29 | Eisai R & D Management Co., Ltd. | Immunomodulatory compounds and methods of use thereof |
GB2348132B (en) * | 1999-03-02 | 2004-08-04 | Nedaa Abdul-Ghani Nasif | Asthma/allergy therapy that targets t-lymphocytes and/or eosinophils |
PT1165778E (en) | 1999-03-11 | 2007-01-31 | Glaxosmithkline Biolog Sa | Uses of casb618 polynucleotides and polypeptides |
ATE399793T1 (en) | 1999-04-02 | 2008-07-15 | Corixa Corp | COMPOUNDS AND METHODS FOR THERAPY AND DIAGNOSIS OF LUNG CANCER |
GB9908885D0 (en) * | 1999-04-19 | 1999-06-16 | Smithkline Beecham Biolog | Vccine |
BRPI0010612B8 (en) * | 1999-04-19 | 2021-05-25 | Smithkline Beecham Biologicals S A | vaccines |
US6558670B1 (en) | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
HUP0201220A3 (en) * | 1999-05-13 | 2004-07-28 | Wyeth Holdings Corp Madison | Adjuvant combination formulations |
US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
GB9918319D0 (en) | 1999-08-03 | 1999-10-06 | Smithkline Beecham Biolog | Vaccine composition |
GB9923176D0 (en) | 1999-09-30 | 1999-12-01 | Smithkline Beecham Biolog | Novel composition |
CA2721011A1 (en) | 1999-10-22 | 2001-05-03 | Aventis Pasteur Limited | Modified gp100 and uses thereof |
IL151097A0 (en) | 2000-02-23 | 2003-04-10 | Smithkline Beecham Biolog | Tumour-specific animal proteins |
US20040002068A1 (en) | 2000-03-01 | 2004-01-01 | Corixa Corporation | Compositions and methods for the detection, diagnosis and therapy of hematological malignancies |
AU5162201A (en) * | 2000-04-13 | 2001-10-30 | Corixa Corporation | Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and qs-21 |
ES2303525T3 (en) | 2000-04-21 | 2008-08-16 | Corixa Corporation | COMPOUNDS AND METHODS FOR THE TREATMENT AND DIAGNOSIS OF INFECTION BY CHLAMYDIA. |
CA2408328C (en) | 2000-05-10 | 2012-04-17 | Aventis Pasteur Limited | Immunogenic polypeptides encoded by mage minigenes and uses thereof |
WO2001097847A1 (en) * | 2000-06-16 | 2001-12-27 | Smithkline Beecham Corporation | Icp27-binding polynucleotides |
ATE442866T1 (en) | 2000-06-20 | 2009-10-15 | Corixa Corp | FUSION PROTEINS FROM MYCOBACTERIUM TUBERCULOSIS |
JP2004513615A (en) | 2000-06-28 | 2004-05-13 | コリクサ コーポレイション | Compositions and methods for treatment and diagnosis of lung cancer |
GB0108364D0 (en) | 2001-04-03 | 2001-05-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
AU8189501A (en) | 2000-06-29 | 2002-01-08 | Smithkline Beecham Biolog | Vaccine composition |
EP1307466B1 (en) | 2000-07-31 | 2005-11-16 | Eisai Co., Ltd. | Immunological adjuvant compounds |
US7229623B1 (en) | 2000-08-03 | 2007-06-12 | Corixa Corporation | Her-2/neu fusion proteins |
UA79735C2 (en) | 2000-08-10 | 2007-07-25 | Глаксосмітклайн Байолоджікалз С.А. | Purification of hbv antigens for use in vaccines |
GB0022742D0 (en) | 2000-09-15 | 2000-11-01 | Smithkline Beecham Biolog | Vaccine |
PT1889630E (en) * | 2000-10-18 | 2012-02-29 | Glaxosmithkline Biolog Sa | Vaccines comprising mage antigen linked to protein d fragment |
GB0025577D0 (en) * | 2000-10-18 | 2000-12-06 | Smithkline Beecham Biolog | Vaccine |
EP1201250A1 (en) * | 2000-10-25 | 2002-05-02 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | Immunogenic compositions comprising liver stage malarial antigens |
SG165981A1 (en) | 2000-10-27 | 2010-11-29 | Chiron Srl | Nucleic acids and proteins from streptococcus groups a & b |
AU2002249764A1 (en) * | 2000-11-16 | 2003-05-06 | Aurx, Inc. | Prevention of recurrent viral disease |
WO2002043486A1 (en) | 2000-11-29 | 2002-06-06 | Xy, Inc. | System for in-vitro fertilization with spermatozoa separated into x-chromosome and y-chromosome bearing populations |
JP2004535765A (en) | 2000-12-07 | 2004-12-02 | カイロン コーポレイション | Endogenous retrovirus up-regulated in prostate cancer |
US7306806B2 (en) | 2001-01-26 | 2007-12-11 | United States Of America As Represented By The Secretary Of The Army | Recombinant P. falciparum merozoite protein-142 vaccine |
EP1409533A2 (en) * | 2001-01-26 | 2004-04-21 | Walter Reed Army Institute of Research | Recombinant plasmodium falciparum merozoite protein-1/42 vaccine |
GB0103171D0 (en) | 2001-02-08 | 2001-03-28 | Smithkline Beecham Biolog | Vaccine composition |
DE60239594D1 (en) | 2001-02-23 | 2011-05-12 | Glaxosmithkline Biolog Sa | INFLUENZA VACCINE COMPOSITIONS FOR INTRADERMAL ADMINISTRATION |
US20030031684A1 (en) | 2001-03-30 | 2003-02-13 | Corixa Corporation | Methods for the production of 3-O-deactivated-4'-monophosphoryl lipid a (3D-MLA) |
GB0109297D0 (en) | 2001-04-12 | 2001-05-30 | Glaxosmithkline Biolog Sa | Vaccine |
WO2002089747A2 (en) | 2001-05-09 | 2002-11-14 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
US20100221284A1 (en) | 2001-05-30 | 2010-09-02 | Saech-Sisches Serumwerk Dresden | Novel vaccine composition |
TWI228420B (en) | 2001-05-30 | 2005-03-01 | Smithkline Beecham Pharma Gmbh | Novel vaccine composition |
GB0115176D0 (en) | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
US20030108565A1 (en) | 2001-07-10 | 2003-06-12 | Johnson Mark E. | Compositions and methods for delivery of proteins and adjuvants encapsulated in microspheres |
GB0118249D0 (en) | 2001-07-26 | 2001-09-19 | Chiron Spa | Histidine vaccines |
CN102294023A (en) * | 2001-07-26 | 2011-12-28 | 奥塔戈创新公司 | Antigenic compositions |
GB0121591D0 (en) | 2001-09-06 | 2001-10-24 | Chiron Spa | Hybrid and tandem expression of neisserial proteins |
GB0118367D0 (en) | 2001-07-27 | 2001-09-19 | Glaxosmithkline Biolog Sa | Novel use |
US20030138434A1 (en) * | 2001-08-13 | 2003-07-24 | Campbell Robert L. | Agents for enhancing the immune response |
US7361352B2 (en) | 2001-08-15 | 2008-04-22 | Acambis, Inc. | Influenza immunogen and vaccine |
AR045702A1 (en) | 2001-10-03 | 2005-11-09 | Chiron Corp | COMPOSITIONS OF ASSISTANTS. |
CA2476755C (en) | 2001-12-17 | 2014-08-26 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of inflammatory bowel disease |
US7030094B2 (en) * | 2002-02-04 | 2006-04-18 | Corixa Corporation | Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and QS-21 |
WO2003070909A2 (en) | 2002-02-20 | 2003-08-28 | Chiron Corporation | Microparticles with adsorbed polypeptide-containing molecules |
US7351413B2 (en) | 2002-02-21 | 2008-04-01 | Lorantis, Limited | Stabilized HBc chimer particles as immunogens for chronic hepatitis |
US20030224013A1 (en) * | 2002-04-19 | 2003-12-04 | Cole Garry T. | Methods for protection against Coccidioides spp. infection using Coccidioides spp. urea amidohydrolase (Ure) protein |
EP2330113B1 (en) | 2002-04-19 | 2016-06-29 | The Governing Council Of The University Of Toronto | Immunological methods and compositions for the treatment of Alzheimer's disease |
EP2302039A1 (en) | 2002-06-13 | 2011-03-30 | Novartis Vaccines and Diagnostics, Inc. | Virus-like particles comprising HML-2 gag polypeptide |
ATE494907T1 (en) | 2002-07-18 | 2011-01-15 | Univ Washington | PHARMACEUTICAL COMPOSITIONS CONTAINING IMMUNOLOGICALLY ACTIVE HERPES SIMPLEX VIRUS PROTEIN FRAGMENTS |
EP1547607A4 (en) * | 2002-08-02 | 2008-11-26 | Dainippon Sumitomo Pharma Co | Bacterial cell wall skeleton component preparation |
CA2493124C (en) | 2002-08-02 | 2014-04-29 | Glaxosmithkline Biologicals S.A. | Vaccine |
GB0220194D0 (en) | 2002-08-30 | 2002-10-09 | Chiron Spa | Improved vesicles |
US7169548B2 (en) | 2002-09-13 | 2007-01-30 | Xy, Inc. | Sperm cell processing and preservation systems |
ATE492288T1 (en) | 2002-10-11 | 2011-01-15 | Novartis Vaccines & Diagnostic | POLYPEPTIDE VACCINES FOR BROAD PROTECTION AGAINST HYPERVIRULENT MENINGOCOCCAL LINES |
EP1569515A4 (en) | 2002-10-23 | 2006-04-26 | Glaxosmithkline Biolog Sa | Methods for vaccinating against malaria |
PT2279746E (en) | 2002-11-15 | 2013-12-09 | Novartis Vaccines & Diagnostic | Surface proteins in neisseria meningitidis |
GB0227346D0 (en) | 2002-11-22 | 2002-12-31 | Chiron Spa | 741 |
AU2004203749A1 (en) | 2003-01-06 | 2004-07-22 | Wyeth | Compositions and methods for diagnosing and treating colon cancers |
JP4827726B2 (en) | 2003-01-30 | 2011-11-30 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス エスアールエル | Injectable vaccine against multiple meningococcal serogroups |
MX347048B (en) | 2003-03-28 | 2017-04-07 | Inguran Llc * | Apparatus, methods and processes for sorting particles and for providing sex-sorted animal sperm. |
PT1613346E (en) | 2003-04-04 | 2013-01-29 | Pah Usa 15 Llc | Microfluidized oil-in-water emulsions and vaccine compositions |
GB0308198D0 (en) | 2003-04-09 | 2003-05-14 | Chiron Srl | ADP-ribosylating bacterial toxin |
US7731967B2 (en) * | 2003-04-30 | 2010-06-08 | Novartis Vaccines And Diagnostics, Inc. | Compositions for inducing immune responses |
ES2596553T3 (en) | 2003-06-02 | 2017-01-10 | Glaxosmithkline Biologicals Sa | Immunogenic compositions based on microparticles comprising adsorbed toxoid and an antigen containing a polysaccharide |
US20060035242A1 (en) | 2004-08-13 | 2006-02-16 | Michelitsch Melissa D | Prion-specific peptide reagents |
CN103357002A (en) | 2003-10-02 | 2013-10-23 | 诺华疫苗和诊断有限公司 | Liquid vaccines for multiple meningococcal serogroups |
GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
ES2541779T3 (en) | 2004-02-05 | 2015-07-24 | The Ohio State University Research Foundation | Chimeric VEGF Peptides |
EP1722815A1 (en) | 2004-03-09 | 2006-11-22 | Chiron Corporation | Influenza virus vaccines |
WO2005102369A1 (en) * | 2004-04-22 | 2005-11-03 | Dainippon Sumitomo Pharma Co., Ltd. | Pharmaceutical preparation containing bacterial cell wall skeleton component |
GB0409745D0 (en) | 2004-04-30 | 2004-06-09 | Chiron Srl | Compositions including unconjugated carrier proteins |
RU2379052C2 (en) | 2004-04-30 | 2010-01-20 | Чирон С.Р.Л. | Meningococcal conjugate vaccination |
GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
GB0410866D0 (en) | 2004-05-14 | 2004-06-16 | Chiron Srl | Haemophilius influenzae |
WO2006078294A2 (en) | 2004-05-21 | 2006-07-27 | Novartis Vaccines And Diagnostics Inc. | Alphavirus vectors for respiratory pathogen vaccines |
EP2497831B1 (en) | 2004-05-25 | 2014-07-16 | Oregon Health and Science University | TB vaccination using HCMV-based vaccine vectors |
US20090263470A1 (en) * | 2004-05-28 | 2009-10-22 | Beth-Ann Coller | Vaccine Compositions Comprising Virosomes and a Saponin Adjuvant |
US8085126B2 (en) * | 2004-07-27 | 2011-12-27 | Honeywell International Inc. | Identification with RFID asset locator for entry authorization |
JP2008508320A (en) | 2004-07-29 | 2008-03-21 | カイロン コーポレイション | Immunogenic composition against gram positive bacteria such as STREPTOCOCCUSAGALACTIAE |
GB0417494D0 (en) | 2004-08-05 | 2004-09-08 | Glaxosmithkline Biolog Sa | Vaccine |
EP1793849A2 (en) | 2004-09-22 | 2007-06-13 | GlaxoSmithKline Biologicals SA | Immunogenic composition for use in vaccination against staphylococcei |
EP2808384B1 (en) | 2004-10-08 | 2017-12-06 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Modulation of replicative fitness by using less frequently used synonymous codons |
GB0424092D0 (en) | 2004-10-29 | 2004-12-01 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
TW200635607A (en) | 2004-12-15 | 2006-10-16 | Elan Pharm Inc | Humanized Aβ antibodies for use in improving cognition |
JP4993750B2 (en) | 2005-01-27 | 2012-08-08 | チルドレンズ ホスピタル アンド リサーチ センター アット オークランド | Vesicular vaccine based on GNA1870 for broad protection against diseases caused by Neisseria meningitidis |
GB0502095D0 (en) | 2005-02-01 | 2005-03-09 | Chiron Srl | Conjugation of streptococcal capsular saccharides |
GB0503337D0 (en) | 2005-02-17 | 2005-03-23 | Glaxosmithkline Biolog Sa | Compositions |
EP1858920B1 (en) | 2005-02-18 | 2016-02-03 | GlaxoSmithKline Biologicals SA | Proteins and nucleic acids from meningitis/sepsis-associated escherichia coli |
SG164344A1 (en) | 2005-02-18 | 2010-09-29 | Novartis Vaccines & Diagnostics Srl | Immunogens from uropathogenic escherichia coli |
GB0504436D0 (en) | 2005-03-03 | 2005-04-06 | Glaxosmithkline Biolog Sa | Vaccine |
PE20061428A1 (en) * | 2005-03-23 | 2007-01-16 | Glaxosmithkline Biolog Sa | VACCINE FORMULATION INCLUDING AN OIL EMULSION ADJUVANT IN WATER AND 3D-MPL |
GB0506001D0 (en) * | 2005-03-23 | 2005-04-27 | Glaxosmithkline Biolog Sa | Novel use |
WO2006104890A2 (en) | 2005-03-31 | 2006-10-05 | Glaxosmithkline Biologicals Sa | Vaccines against chlamydial infection |
CN101355928B (en) * | 2005-04-26 | 2013-05-22 | 卫材R&D管理株式会社 | Compositions and methods for cancer immunotherapy |
US20070292418A1 (en) * | 2005-04-26 | 2007-12-20 | Eisai Co., Ltd. | Compositions and methods for immunotherapy |
US7691396B2 (en) | 2005-06-15 | 2010-04-06 | The Ohio State University Research Foundation | Chimeric peptides comprising HER-2 B-cell epitopes and measles virus fusion protein T-cell epitopes |
EP2305701A1 (en) | 2005-07-01 | 2011-04-06 | Forsyth Dental Infirmary for Children | Tuberculosis antigen detection assays and vaccines |
EP1928539A1 (en) * | 2005-09-30 | 2008-06-11 | Tti Ellebeau, Inc. | Functionalized microneedles transdermal drug delivery systems, devices, and methods |
KR20080066712A (en) * | 2005-09-30 | 2008-07-16 | 티티아이 엘뷰 가부시키가이샤 | Functionalized microneedles transdermal drug delivery systems, devices, and methods |
GB0519871D0 (en) | 2005-09-30 | 2005-11-09 | Secr Defence | Immunogenic agents |
WO2007041314A2 (en) * | 2005-09-30 | 2007-04-12 | Tti Ellebeau, Inc. | Transdermal drug delivery systems, devices, and methods employing novel pharmaceutical vehicles |
WO2007047749A1 (en) | 2005-10-18 | 2007-04-26 | Novartis Vaccines And Diagnostics Inc. | Mucosal and systemic immunizations with alphavirus replicon particles |
CA2628206A1 (en) | 2005-11-04 | 2007-05-10 | Novartis Vaccines And Diagnostics S.R.L. | Influenza vaccine with reduced amount of oil-in-water emulsion as adjuvant |
JP2009514839A (en) | 2005-11-04 | 2009-04-09 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス エスアールエル | Adjuvant influenza vaccine containing cytokine inducer |
BRPI0618254A2 (en) * | 2005-11-04 | 2011-08-23 | Novartis Vaccines & Diagnostic | free aqueous phase surfactant emulsions to provide adjuvant to split influenza vaccines |
GB0522765D0 (en) | 2005-11-08 | 2005-12-14 | Chiron Srl | Combination vaccine manufacture |
AU2006338570B2 (en) * | 2005-11-18 | 2013-07-11 | The Ohio State University Research Foundation | Viral gene products and methods for vaccination to prevent viral associated diseases |
WO2007061964A1 (en) * | 2005-11-18 | 2007-05-31 | 3M Innovative Properties Company | Methods for coating microneedles |
WO2007081447A2 (en) | 2005-11-22 | 2007-07-19 | Novartis Vaccines And Diagnostics, Inc. | Norovirus and sapovirus antigens |
GB0524066D0 (en) | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
GB0607088D0 (en) | 2006-04-07 | 2006-05-17 | Glaxosmithkline Biolog Sa | Vaccine |
JO2813B1 (en) | 2005-12-22 | 2014-09-15 | جلاكسو سميث كلاين بايولوجيكالز اس.ايه | Pneumococcal polysaccharide conjugate vaccine |
US20080033398A1 (en) * | 2005-12-29 | 2008-02-07 | Transcutaneous Technologies Inc. | Device and method for enhancing immune response by electrical stimulation |
JP6087041B2 (en) | 2006-01-27 | 2017-03-08 | ノバルティス アーゲー | Influenza virus vaccine containing hemagglutinin and matrix protein |
CA2646539A1 (en) | 2006-03-23 | 2007-09-27 | Novartis Ag | Imidazoquinoxaline compounds as immunomodulators |
CA2646891A1 (en) | 2006-03-23 | 2007-09-27 | Novartis Ag | Immunopotentiating compounds |
WO2007110776A1 (en) | 2006-03-24 | 2007-10-04 | Novartis Vaccines And Diagnostics Gmbh & Co Kg | Storage of influenza vaccines without refrigeration |
MX337528B (en) | 2006-03-30 | 2016-03-09 | Glaxosmithkline Biolog Sa | Immunogenic composition. |
CN101460192A (en) | 2006-03-30 | 2009-06-17 | 恩布里克斯公司 | Methods and compositions for vaccination of poultry |
US10138279B2 (en) | 2006-04-13 | 2018-11-27 | Regents Of The University Of Michigan | Compositions and methods for Bacillus anthracis vaccination |
US9839685B2 (en) | 2006-04-13 | 2017-12-12 | The Regents Of The University Of Michigan | Methods of inducing human immunodeficiency virus-specific immune responses in a host comprising nasally administering compositions comprising a naonemulsion and recombinant GP120 immunogen |
TW200806315A (en) | 2006-04-26 | 2008-02-01 | Wyeth Corp | Novel formulations which stabilize and inhibit precipitation of immunogenic compositions |
ES2539042T3 (en) | 2006-06-02 | 2015-06-25 | Glaxosmithkline Biologicals S.A. | Identification procedure of whether a patient will respond to immunotherapy or not |
ATE522541T1 (en) | 2006-06-09 | 2011-09-15 | Novartis Ag | BACTERIAL ADHESIN CONFORMERS |
JP5275982B2 (en) | 2006-06-12 | 2013-08-28 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | vaccine |
US8153116B2 (en) | 2006-07-11 | 2012-04-10 | University Of Connecticut | Use of conditional plasmodium strains lacking an essential gene in malaria vaccination |
WO2008094183A2 (en) * | 2006-07-11 | 2008-08-07 | University Of Connecticut | Use of conditional plasmodium strains lacking nutrient transporters in malaria vaccination |
MX2009000660A (en) * | 2006-07-17 | 2009-04-08 | Glaxosmithkline Biolog Sa | Influenza vaccine. |
SI2422810T1 (en) | 2006-07-17 | 2015-01-30 | Glaxosmithkline Biologicals S.A. | Influenza vaccine |
SG173377A1 (en) | 2006-07-18 | 2011-08-29 | Glaxosmithkline Biolog Sa | Vaccines for malaria |
GB0614460D0 (en) | 2006-07-20 | 2006-08-30 | Novartis Ag | Vaccines |
WO2008012538A2 (en) | 2006-07-25 | 2008-01-31 | The Secretary Of State For Defence | Live vaccine strains of francisella |
EP2586790A3 (en) | 2006-08-16 | 2013-08-14 | Novartis AG | Immunogens from uropathogenic Escherichia coli |
EP2066344B2 (en) | 2006-09-07 | 2016-06-29 | GlaxoSmithKline Biologicals S.A. | Inactivated Poliovirus combination vaccine |
ES2536401T3 (en) | 2006-09-11 | 2015-05-25 | Novartis Ag | Making vaccines against influenza viruses without using eggs |
EP2433648A3 (en) | 2006-10-12 | 2012-04-04 | GlaxoSmithKline Biologicals S.A. | Vaccine comprising an oil in water emulsion adjuvant |
BRPI0717219B8 (en) * | 2006-10-12 | 2021-05-25 | Glaxosmithkline Biologicals Sa | immunogenic composition, and, use of an immunogenic composition |
GB0622282D0 (en) | 2006-11-08 | 2006-12-20 | Novartis Ag | Quality control methods |
ES2480491T3 (en) | 2006-12-06 | 2014-07-28 | Novartis Ag | Vaccines including four influenza virus strains antigen |
MX362698B (en) | 2007-03-02 | 2019-02-01 | Glaxosmithkline Biologicals Sa | NOVEL METHOD and COMPOSITIONS. |
MX351247B (en) | 2007-04-04 | 2017-10-05 | Infectious Disease Res Institute Star | Immunogenic compositions comprising mycobacterium tuberculosis polypeptides and fusions thereof. |
US9452209B2 (en) | 2007-04-20 | 2016-09-27 | Glaxosmithkline Biologicals Sa | Influenza vaccine |
EA201490303A1 (en) | 2007-05-02 | 2014-05-30 | Глаксосмитклайн Байолоджикалс С.А. | VACCINE |
GB0711858D0 (en) * | 2007-06-19 | 2007-07-25 | Glaxosmithkline Biolog Sa | Vaccine |
PT2167121E (en) | 2007-06-26 | 2015-12-02 | Glaxosmithkline Biolog Sa | Vaccine comprising streptococcus pneumoniae capsular polysaccharide conjugates |
BRPI0813866A2 (en) | 2007-06-27 | 2015-01-06 | Novartis Ag | VACCINES AGAINST INFLUENCE WITH LOW ADDITIVE CONTENT |
GB0713880D0 (en) | 2007-07-17 | 2007-08-29 | Novartis Ag | Conjugate purification |
GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
ES2539818T3 (en) | 2007-08-02 | 2015-07-06 | Biondvax Pharmaceuticals Ltd. | Multimeric multi-epitopic flu vaccines |
WO2009020553A2 (en) | 2007-08-03 | 2009-02-12 | President And Fellows Of Harvard College | Chlamydia antigens |
ES2561483T3 (en) | 2007-09-12 | 2016-02-26 | Glaxosmithkline Biologicals Sa | GAS57 mutant antigens and GAS57 antibodies |
KR20100085917A (en) | 2007-09-17 | 2010-07-29 | 온코메틸롬 사이언시즈 에스에이 | Improved detection of mage-a expression |
JO3076B1 (en) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | Immunotherapy regimes dependent on apoe status |
GB0810305D0 (en) | 2008-06-05 | 2008-07-09 | Novartis Ag | Influenza vaccination |
EP2227250A4 (en) | 2007-12-03 | 2011-07-06 | Harvard College | Chlamydia antigens |
EP2227251A1 (en) * | 2007-12-06 | 2010-09-15 | GlaxoSmithKline Biologicals SA | Influenza composition |
JP2011506334A (en) * | 2007-12-07 | 2011-03-03 | ノバルティス アーゲー | Composition for inducing an immune response |
WO2009117035A1 (en) | 2007-12-19 | 2009-09-24 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Soluble forms of hendra and nipah virus f glycoprotein and uses thereof |
GB0818453D0 (en) | 2008-10-08 | 2008-11-12 | Novartis Ag | Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom |
KR101773114B1 (en) | 2007-12-21 | 2017-08-30 | 노파르티스 아게 | Mutant forms of streptolysin o |
US8092813B1 (en) | 2007-12-28 | 2012-01-10 | Novartis Ag | Polychlorinated biphenyls and squalene-containing adjuvants |
ES2532946T3 (en) | 2008-02-21 | 2015-04-06 | Novartis Ag | Meningococcal PUfH polypeptides |
EP2265640B1 (en) | 2008-03-10 | 2015-11-04 | Children's Hospital & Research Center at Oakland | Chimeric factor h binding proteins (fhbp) containing a heterologous b domain and methods of use |
US20110117131A1 (en) * | 2008-04-09 | 2011-05-19 | Ning Huang | Production of OspA for Lyme Disease Control |
AU2009237647A1 (en) | 2008-04-16 | 2009-10-22 | Glaxosmithkline Biologicals S.A. | Vaccine |
WO2009129502A2 (en) | 2008-04-18 | 2009-10-22 | The General Hospital Corporation | Immunotherapies employing self-assembling vaccines |
CA2725329C (en) | 2008-05-23 | 2013-10-01 | The Regents Of The University Of Michigan | Nanoemulsion vaccines |
US9114098B2 (en) | 2008-06-04 | 2015-08-25 | The Chemo-Sero-Therapeutic Research Institute | Method for using inactivated Japanese encephalitis virus particles as adjuvant |
KR101701198B1 (en) | 2008-06-19 | 2017-02-01 | 배리에이션 바이오테크놀로지스 아이엔씨. | Compositions and methods for treating influenza |
CA2733356C (en) | 2008-08-01 | 2016-06-07 | Gamma Vaccines Pty Limited | Influenza vaccines |
GB0815872D0 (en) | 2008-09-01 | 2008-10-08 | Pasteur Institut | Novel method and compositions |
WO2010036945A2 (en) | 2008-09-26 | 2010-04-01 | The Regents Of The University Of Michigan | Nanoemulsion therapeutic compositions and methods of using the same |
US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
WO2010057197A1 (en) | 2008-11-17 | 2010-05-20 | The Regents Of The University Of Michigan | Cancer vaccine compositions and methods of using the same |
GB0822001D0 (en) * | 2008-12-02 | 2009-01-07 | Glaxosmithkline Biolog Sa | Vaccine |
CN102239253A (en) | 2008-12-03 | 2011-11-09 | 普罗蒂亚维仕尼科技有限公司 | Glutamyl trna synthetase (GTS) fragments |
SG10201400388QA (en) | 2008-12-09 | 2014-05-29 | Pfizer Vaccines Llc | IgE CH3 peptide vaccine |
CN107365751B (en) | 2008-12-16 | 2021-07-09 | 纳米医疗公司 | Production of influenza vaccines |
US8465751B2 (en) | 2009-01-12 | 2013-06-18 | Novartis Ag | Cna—B domain antigens in vaccines against gram positive bacteria |
GB0900455D0 (en) | 2009-01-13 | 2009-02-11 | Secr Defence | Vaccine |
GB0901411D0 (en) | 2009-01-29 | 2009-03-11 | Secr Defence | Treatment |
GB0901423D0 (en) | 2009-01-29 | 2009-03-11 | Secr Defence | Treatment |
US20100234283A1 (en) | 2009-02-04 | 2010-09-16 | The Ohio State University Research Foundation | Immunogenic epitopes, peptidomimetics, and anti-peptide antibodies, and methods of their use |
US9265821B2 (en) * | 2009-02-17 | 2016-02-23 | Glaxosmithkline Biologicals Sa | Inactivated dengue virus vaccine with aluminium-free adjuvant |
EP3549602A1 (en) | 2009-03-06 | 2019-10-09 | GlaxoSmithKline Biologicals S.A. | Chlamydia antigens |
JP2012520663A (en) | 2009-03-17 | 2012-09-10 | エムディーエックスヘルス エスエー | Improved detection of gene expression |
GB0906234D0 (en) | 2009-04-14 | 2009-05-20 | Secr Defence | Vaccine |
SI2510947T1 (en) | 2009-04-14 | 2016-05-31 | Glaxosmithkline Biologicals S.A. | Compositions for immunising against Staphylococcus aureus |
EP2424562B1 (en) | 2009-04-30 | 2015-10-07 | Coley Pharmaceutical Group, Inc. | Pneumococcal vaccine and uses thereof |
WO2010132833A1 (en) | 2009-05-14 | 2010-11-18 | The Regents Of The University Of Michigan | Streptococcus vaccine compositions and methods of using the same |
EA020617B1 (en) | 2009-05-27 | 2014-12-30 | Глаксосмитклайн Байолоджикалс С.А. | Casb7439 constructs |
CA2765364C (en) | 2009-06-15 | 2015-05-26 | National University Of Singapore | Influenza vaccine, composition, and methods of use |
WO2010148111A1 (en) | 2009-06-16 | 2010-12-23 | The Regents Of The University Of Michigan | Nanoemulsion vaccines |
CA2803282C (en) | 2009-07-06 | 2018-05-01 | David E. Anderson | Methods for preparing vesicles and formulations produced therefrom |
JP5854559B2 (en) | 2009-07-06 | 2016-02-09 | ヴァリエーション バイオテクノロジーズ インコーポレイテッド | Method for preparing vesicles and preparations produced therefrom |
CA2767536A1 (en) | 2009-07-07 | 2011-01-13 | Novartis Ag | Conserved escherichia coli immunogens |
BR112012001666A2 (en) | 2009-07-15 | 2019-09-24 | Novartis Ag | rsv f protein compositions and methods for making the same |
JP2012532626A (en) | 2009-07-16 | 2012-12-20 | ノバルティス アーゲー | Detoxified Escherichia coli immunogen |
KR101425404B1 (en) | 2009-07-17 | 2014-08-01 | 한림대학교 산학협력단 | Immunostimulatory Compositions Comprising Liposome―Encapsulated Oligonucleotides and Epitopes |
SG177637A1 (en) | 2009-07-30 | 2012-03-29 | Pfizer Vaccines Llc | Antigenic tau peptides and uses thereof |
GB0913680D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
GB0913681D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
CN102596240B (en) | 2009-08-27 | 2015-02-04 | 诺华股份有限公司 | Hybrid polypeptides including meningococcal fHBP sequences |
SG10201401516XA (en) | 2009-09-03 | 2014-10-30 | Pfizer Vaccines Llc | Pcsk9 vaccine |
PL2475384T3 (en) * | 2009-09-10 | 2017-02-28 | Merial, Inc. | New vaccine formulations comprising saponin-containing adjuvants |
US20120237536A1 (en) | 2009-09-10 | 2012-09-20 | Novartis | Combination vaccines against respiratory tract diseases |
GB0917457D0 (en) | 2009-10-06 | 2009-11-18 | Glaxosmithkline Biolog Sa | Method |
GB0917002D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Improved shigella blebs |
GB0917003D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Purification of bacterial vesicles |
CN102724988B (en) | 2009-09-30 | 2014-09-10 | 诺华股份有限公司 | Expression of meningococcal fHBP polypeptides |
CA2779798C (en) | 2009-09-30 | 2019-03-19 | Novartis Ag | Conjugation of staphylococcus aureus type 5 and type 8 capsular polysaccharides |
EP2485753A4 (en) | 2009-10-09 | 2013-12-11 | Cbio Ltd | Chaperonin 10 variants |
GB0918392D0 (en) | 2009-10-20 | 2009-12-02 | Novartis Ag | Diagnostic and therapeutic methods |
MX2012004850A (en) | 2009-10-27 | 2012-05-22 | Novartis Ag | Modified meningococcal fhbp polypeptides. |
GB0918830D0 (en) | 2009-10-27 | 2009-12-09 | Glaxosmithkline Biolog Niederl | Process |
GB0919117D0 (en) | 2009-10-30 | 2009-12-16 | Glaxosmithkline Biolog Sa | Process |
GB0919690D0 (en) | 2009-11-10 | 2009-12-23 | Guy S And St Thomas S Nhs Foun | compositions for immunising against staphylococcus aureus |
WO2011067758A2 (en) | 2009-12-02 | 2011-06-09 | Protea Vaccine Technologies Ltd. | Immunogenic fragments and multimers from streptococcus pneumoniae proteins |
US20110159031A1 (en) | 2009-12-22 | 2011-06-30 | Baxter International Inc. | Vaccine to Influenza A Virus |
NZ629256A (en) | 2009-12-22 | 2016-02-26 | Celldex Therapeutics Inc | Vaccine compositions |
ES2707778T3 (en) | 2009-12-30 | 2019-04-05 | Glaxosmithkline Biologicals Sa | Immunogens polysaccharides conjugated with carrier proteins of E. coli |
EP2353609A1 (en) | 2010-02-04 | 2011-08-10 | Sanofi Pasteur | Immunization compositions and methods |
GB201003333D0 (en) | 2010-02-26 | 2010-04-14 | Novartis Ag | Immunogenic proteins and compositions |
GB201003920D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Method of treatment |
GB201003924D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Immunogenic composition |
CN103002910A (en) | 2010-03-10 | 2013-03-27 | 葛兰素史密丝克莱恩生物有限公司 | Vaccine composition |
CN102946900A (en) | 2010-03-11 | 2013-02-27 | 免疫设计公司 | Vaccines for pandemic influenza |
AU2011231574A1 (en) | 2010-03-26 | 2012-10-11 | Glaxosmithkline Biologicals S.A. | HIV vaccine |
BR122022015250B1 (en) | 2010-03-30 | 2023-11-07 | Children´S Hospital & Research Center At Oakland | IMMUNOGENIC COMPOSITIONS AND THEIR USES |
GB201005625D0 (en) | 2010-04-01 | 2010-05-19 | Novartis Ag | Immunogenic proteins and compositions |
JP2013529894A (en) | 2010-04-07 | 2013-07-25 | ノバルティス アーゲー | Method for generating parvovirus B19 virus-like particles |
GB201006324D0 (en) | 2010-04-15 | 2010-06-02 | Glaxosmithkline Biolog Sa | Vaccine |
KR20130121699A (en) | 2010-05-28 | 2013-11-06 | 테트리스 온라인, 인코포레이티드 | Interactive hybrid asynchronous computer game infrastructure |
CN102933229A (en) | 2010-06-04 | 2013-02-13 | 惠氏有限责任公司 | Vaccine formulations |
EP2942061A3 (en) | 2010-06-07 | 2016-01-13 | Pfizer Vaccines LLC | Ige ch3 peptide vaccine |
US8895017B2 (en) | 2010-06-07 | 2014-11-25 | Pfizer Inc. | HER-2 peptides and vaccines |
GB201009861D0 (en) | 2010-06-11 | 2010-07-21 | Novartis Ag | OMV vaccines |
US8658603B2 (en) | 2010-06-16 | 2014-02-25 | The Regents Of The University Of Michigan | Compositions and methods for inducing an immune response |
US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
WO2012006293A1 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Norovirus derived immunogenic compositions and methods |
CA2840079C (en) | 2010-07-06 | 2018-07-03 | Variation Biotechnologies Inc. | Compositions and methods for treating influenza |
GB201015132D0 (en) | 2010-09-10 | 2010-10-27 | Univ Bristol | Vaccine composition |
GB201101665D0 (en) | 2011-01-31 | 2011-03-16 | Novartis Ag | Immunogenic compositions |
US20130259948A1 (en) | 2010-09-21 | 2013-10-03 | National Institute Of Immunology | Spray dried powder formulation for vaccines entrapping alum and the antigen in biodegradable polymer particles |
MX354752B (en) | 2010-09-27 | 2018-03-20 | Janssen Vaccines & Prevention Bv | Heterologous prime boost vaccination regimen against malaria. |
JP2014501225A (en) | 2010-09-27 | 2014-01-20 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | vaccine |
GB201017519D0 (en) | 2010-10-15 | 2010-12-01 | Novartis Vaccines Inst For Global Health S R L | Vaccines |
GB201101331D0 (en) | 2011-01-26 | 2011-03-09 | Glaxosmithkline Biolog Sa | Compositions and uses |
US20130345079A1 (en) | 2010-10-27 | 2013-12-26 | Infectious Disease Research Institute | Mycobacterium tuberculosis antigens and combinations thereof having high seroreactivity |
ES2859673T3 (en) | 2010-11-08 | 2021-10-04 | Infectious Disease Res Inst | Vaccines comprising nonspecific nucleoside hydrolase polypeptides and sterol 24-c-methyltransferase (SMT) for the treatment and diagnosis of leishmaniasis |
WO2012072769A1 (en) | 2010-12-01 | 2012-06-07 | Novartis Ag | Pneumococcal rrgb epitopes and clade combinations |
EP2646459B1 (en) | 2010-12-02 | 2020-01-08 | Bionor Immuno AS | Peptide scaffold design |
GB201022007D0 (en) | 2010-12-24 | 2011-02-02 | Imp Innovations Ltd | DNA-sensor |
WO2012085668A2 (en) | 2010-12-24 | 2012-06-28 | Novartis Ag | Compounds |
JP6294076B2 (en) | 2011-01-06 | 2018-03-14 | ビオノール イミュノ エーエスBionor Immuno As | Multimeric peptide |
MX357319B (en) | 2011-01-13 | 2018-07-04 | Variation Biotechnologies Inc | Methods for preparing vesicles and formulations produced therefrom. |
US10736844B2 (en) | 2011-01-13 | 2020-08-11 | Variation Biotechnologies Inc. | Compositions and methods for treating viral infections |
SI2667892T1 (en) | 2011-01-26 | 2019-05-31 | Glaxosmithkline Biologicals Sa | Rsv immunization regimen |
EP2667891B1 (en) | 2011-01-27 | 2021-10-06 | Gamma Vaccines Pty Limited | Combination vaccines |
AU2011360572B2 (en) | 2011-02-22 | 2017-03-02 | Biondvax Pharmaceuticals Ltd. | Multimeric multiepitope polypeptides in improved seasonal and pandemic influenza vaccines |
WO2012131504A1 (en) | 2011-03-02 | 2012-10-04 | Pfizer Inc. | Pcsk9 vaccine |
US9321813B2 (en) | 2011-03-29 | 2016-04-26 | Uab Research Foundation | Methods and compositions for cytomegalovirus IL-10 protein |
TW201302779A (en) | 2011-04-13 | 2013-01-16 | Glaxosmithkline Biolog Sa | Fusion proteins & combination vaccines |
US20120288515A1 (en) | 2011-04-27 | 2012-11-15 | Immune Design Corp. | Synthetic long peptide (slp)-based vaccines |
ES2651143T3 (en) | 2011-05-13 | 2018-01-24 | Glaxosmithkline Biologicals Sa | RS prefusion F antigens |
US20140072622A1 (en) | 2011-05-17 | 2014-03-13 | Glaxosmithkline Biologicals S.A. | Vaccine against streptococcus pneumoniae |
US20130156803A1 (en) | 2011-06-04 | 2013-06-20 | Rochester General Hospital Research Institute | Compositions and methods related to p6 |
WO2012177595A1 (en) | 2011-06-21 | 2012-12-27 | Oncofactor Corporation | Compositions and methods for the therapy and diagnosis of cancer |
WO2013006569A2 (en) * | 2011-07-01 | 2013-01-10 | The Regents Of The University Of California | Herpes virus vaccine and methods of use |
WO2013016460A1 (en) | 2011-07-25 | 2013-01-31 | Novartis Ag | Compositions and methods for assessing functional immunogenicity of parvovirus vaccines |
GB201113570D0 (en) | 2011-08-05 | 2011-09-21 | Glaxosmithkline Biolog Sa | Vaccine |
WO2013028738A1 (en) | 2011-08-22 | 2013-02-28 | Nanobio Corporation | Herpes simplex virus nanoemulsion vaccine |
GB201114919D0 (en) | 2011-08-30 | 2011-10-12 | Glaxosmithkline Biolog Sa | Method |
GB201114923D0 (en) | 2011-08-30 | 2011-10-12 | Novartis Ag | Immunogenic proteins and compositions |
CN104093421A (en) | 2011-09-09 | 2014-10-08 | 纳诺碧欧公司 | Nanoemulsion respiratory syncytial virus (RSV) subunit vaccine |
CN103917245B (en) | 2011-09-14 | 2017-06-06 | 葛兰素史密丝克莱恩生物有限公司 | Method for preparing glycoprotein glycoconjugate |
WO2013038385A2 (en) | 2011-09-14 | 2013-03-21 | Novartis Ag | Escherichia coli vaccine combination |
MX2014002769A (en) | 2011-09-16 | 2014-06-11 | Ucb Pharma Sa | Neutralising antibodies to the major exotoxins tcda and tcdb of clostridium difficile. |
US20130122038A1 (en) | 2011-11-14 | 2013-05-16 | The United States Of America As Represented By The Secretary Of The Department | Heterologous prime-boost immunization using measles virus-based vaccines |
CN104066447A (en) | 2011-11-23 | 2014-09-24 | 拜奥文斯瑞有限公司 | Recombinant proteins and their therapeutic uses |
EP2788477A2 (en) | 2011-12-07 | 2014-10-15 | Institut Pasteur | Identification of a swine parecho-like virus and applications |
RU2014127714A (en) | 2011-12-08 | 2016-01-27 | Новартис Аг | TOXIN VACCINE Clostridium difficile |
EP2802353A4 (en) | 2012-01-12 | 2015-12-02 | Variation Biotechnologies Inc | Compositions and methods for treating viral infections |
WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
AU2013213345A1 (en) | 2012-01-27 | 2014-08-28 | Variation Biotechnologies, Inc. | Methods and compositions for therapeutic agents |
CA2865028A1 (en) | 2012-02-24 | 2013-08-29 | Novartis Ag | Pilus proteins and compositions |
WO2013134577A2 (en) | 2012-03-08 | 2013-09-12 | Detectogen, Inc. | Leishmaniasis antigen detection assays and vaccines |
GB201205189D0 (en) | 2012-03-23 | 2012-05-09 | Glaxosmithkline Biolog Sa | Novel medical use |
ES2685612T3 (en) | 2012-03-23 | 2018-10-10 | Pitney Pharmaceuticals Pty Limited | Kinase inhibitors for cancer treatment |
ES2702278T3 (en) | 2012-04-01 | 2019-02-28 | Technion Res & Dev Foundation | Extracellular matrix metalloproteinase (emmprin) inducer peptides and binding antibodies |
US9821050B2 (en) | 2012-04-02 | 2017-11-21 | The University Of North Carolina At Chapel Hill | Chimeric dengue virus E glycoproteins comprising mutant domain I and domain II hinge regions |
US10279026B2 (en) | 2012-04-26 | 2019-05-07 | Glaxosmithkline Biologicals Sa | Antigens and antigen combinations |
BR112014026812A8 (en) | 2012-04-26 | 2022-10-04 | Novartis Ag | ANTIGENS AND ANTIGEN COMBINATIONS |
EP2659908A1 (en) | 2012-05-01 | 2013-11-06 | Affiris AG | Compositions |
EP2659906A1 (en) | 2012-05-01 | 2013-11-06 | Affiris AG | Compositions |
EP2659907A1 (en) | 2012-05-01 | 2013-11-06 | Affiris AG | Compositions |
DK2844282T3 (en) | 2012-05-04 | 2019-07-15 | Pfizer | PROSTATA ASSOCIATED ANTIGENES AND VACCINE-BASED IMMUNTERAPIREGIMENES |
MX2014014067A (en) | 2012-05-22 | 2015-02-04 | Novartis Ag | Meningococcus serogroup x conjugate. |
EP2666785A1 (en) | 2012-05-23 | 2013-11-27 | Affiris AG | Complement component C5a-based vaccine |
CA2875683A1 (en) | 2012-06-05 | 2013-12-12 | The Australian National University | Vaccination with interleukin-4 antagonists |
CA2874923C (en) | 2012-06-06 | 2021-08-31 | Bionor Immuno As | Peptides derived from viral proteins for use as immunogens and dosage reactants |
MY168959A (en) | 2012-07-24 | 2019-01-28 | Sanofi Pasteur | Vaccine compositions for the prevention of dengue virus infection |
WO2014016362A1 (en) | 2012-07-24 | 2014-01-30 | Sanofi Pasteur | Vaccine compositions for prevention against dengue virus infection |
JP6523955B2 (en) | 2012-08-01 | 2019-06-05 | バヴァリアン・ノルディック・アクティーゼルスカブ | Recombinant modified vaccinia virus Ankara (MVA) RS virus (RSV) vaccine |
JP2015525784A (en) | 2012-08-03 | 2015-09-07 | インフェクティアス ディジーズ リサーチ インスティチュート | Compositions and methods for treating active tuberculosis infection |
EP2880014B1 (en) | 2012-08-06 | 2017-05-17 | Pitney Pharmaceuticals Pty Limited | Compounds for the treatment of mtor pathway related diseases |
JP2014040396A (en) * | 2012-08-23 | 2014-03-06 | Chemo-Sero-Therapeutic Research Institute | Adjuvant composition containing dyslipidemia therapeutic agent |
EP2703483A1 (en) | 2012-08-29 | 2014-03-05 | Affiris AG | PCSK9 peptide vaccine |
US10232035B2 (en) | 2012-09-14 | 2019-03-19 | The Regents Of The University Of Colorado, A Body Corporate | Conditionally replication deficient herpes virus and use thereof in vaccines |
EP3400960A1 (en) | 2012-09-18 | 2018-11-14 | GlaxoSmithKline Biologicals S.A. | Outer membrane vesicles |
WO2014053521A2 (en) | 2012-10-02 | 2014-04-10 | Novartis Ag | Nonlinear saccharide conjugates |
CN104717977A (en) | 2012-10-03 | 2015-06-17 | 诺华股份有限公司 | Immunogenic composition |
US9982034B2 (en) | 2012-10-24 | 2018-05-29 | Platelet Targeted Therapeutics, Llc | Platelet targeted treatment |
BR112015012515B1 (en) | 2012-11-30 | 2023-04-11 | Sanofi Pasteur | USE OF ANTIGENS, NUCLEIC ACID CONSTRUCTS OR VIRAL VECTORS CAPABLE OF EXPRESSING A VIRUS-LIKE PARTICLE (VLP) OF DENGUE AND A VACCINE AGAINST MEASLES, A VACCINE AGAINST MUMPS AND A VACCINE AGAINST RUBELLA |
CN111249455A (en) | 2012-11-30 | 2020-06-09 | 葛兰素史密丝克莱恩生物有限公司 | Pseudomonas antigens and antigen combinations |
CN112807422A (en) | 2012-12-05 | 2021-05-18 | 葛兰素史密丝克莱恩生物有限公司 | Immunogenic compositions |
JP6502853B2 (en) | 2012-12-17 | 2019-04-17 | ニューサウス イノベイションズ ピーティーワイ リミテッド | Treatment of diseases in which mucin is involved |
CA2934958A1 (en) | 2012-12-24 | 2014-07-03 | Cell Ideas Pty Ltd | Vaccines for the treatment of cancer and compositions for enhancing vaccine efficacy |
WO2014124228A1 (en) | 2013-02-07 | 2014-08-14 | Children's Medical Center Corporation | Protein antigens that provide protection against pneumococcal colonization and/or disease |
EP2970409A2 (en) | 2013-03-15 | 2016-01-20 | Bioven 3 Limited | Self-assembling synthetic proteins |
ES2728865T3 (en) | 2013-03-28 | 2019-10-29 | Infectious Disease Res Inst | Vaccines comprising Leishmania polypeptides for the treatment and diagnosis of leishmaniasis |
WO2014182872A1 (en) | 2013-05-08 | 2014-11-13 | Protatek International, Inc. | Vaccine for pcv2 and mycoplasma |
EP2996718B1 (en) | 2013-05-15 | 2020-01-15 | The Governors of the University of Alberta | E1e2 hcv vaccines and methods of use |
GB201310008D0 (en) | 2013-06-05 | 2013-07-17 | Glaxosmithkline Biolog Sa | Immunogenic composition for use in therapy |
BR112015032388A8 (en) | 2013-06-26 | 2020-01-14 | Univ North Carolina Chapel Hill | glycoprotein and chimeric dengue virus, their uses, flavivirus particle, isolated nucleic acid molecule, and compositions |
US10364277B2 (en) | 2013-07-01 | 2019-07-30 | Newsouth Innovations Pty Limited | Diagnosis and treatment of autoimmune diseases |
ES2739123T3 (en) | 2013-08-28 | 2020-01-29 | Glaxosmithkline Biologicals Sa | New flu antigens and antibodies |
CN104436157A (en) | 2013-09-23 | 2015-03-25 | 恩金生物有限公司 | Influenza vaccine and therapy |
JP6306700B2 (en) | 2013-11-01 | 2018-04-04 | ユニバーシティ オブ オスロUniversity of Oslo | Modified albumin and use thereof |
US9993541B2 (en) | 2013-11-13 | 2018-06-12 | University Of Oslo | Outer membrane vesicles and uses thereof |
EP3069138B1 (en) | 2013-11-15 | 2019-01-09 | Oslo Universitetssykehus HF | Ctl peptide epitopes and antigen-specific t cells, methods for their discovery, and uses thereof |
WO2015077442A2 (en) | 2013-11-20 | 2015-05-28 | La Jolla Institute For Allergy And Immunology | Grass pollen immunogens and methods and uses for immune response modulation |
WO2015077434A2 (en) | 2013-11-20 | 2015-05-28 | La Jolla Institute For Allergy And Immunology | Pan pollen immunogens and methods and uses for immune response modulation |
WO2015092710A1 (en) | 2013-12-19 | 2015-06-25 | Glaxosmithkline Biologicals, S.A. | Contralateral co-administration of vaccines |
EA201691348A1 (en) | 2013-12-31 | 2016-11-30 | Инфекшес Дизиз Рисерч Инститьют | ONE-FLAKE VACCINE COMPOSITIONS |
US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
CA2935722A1 (en) | 2014-01-21 | 2015-07-30 | Immune Design Corp. | Compositions for use in the treatment of allergic conditions |
PE20212335A1 (en) | 2014-01-21 | 2021-12-16 | Pfizer | IMMUNOGENIC COMPOSITIONS COMPRISING CONJUGATED CAPSULAR SACCHARIDE ANTIGENS AND USES THEREOF |
WO2015123291A1 (en) | 2014-02-11 | 2015-08-20 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Pcsk9 vaccine and methods of using the same |
TW201620927A (en) | 2014-02-24 | 2016-06-16 | 葛蘭素史密斯克藍生物品公司 | USPA2 protein constructs and uses thereof |
WO2015131053A1 (en) | 2014-02-28 | 2015-09-03 | Alk-Abelló A/S | Polypeptides derived from phl p and methods and uses thereof for immune response modulation |
JP6550072B2 (en) | 2014-04-03 | 2019-07-24 | バイオンドバックス ファーマシューティカルズ リミテッド | Compositions of multimeric multi-epitope influenza polypeptides and their production |
MA47849A (en) | 2014-05-28 | 2020-01-29 | Agenus Inc | ANTI-GITR ANTIBODIES AND THEIR METHODS OF USE |
TW201623329A (en) | 2014-06-30 | 2016-07-01 | 亞佛瑞司股份有限公司 | Vaccines and monoclonal antibodies targeting truncated variants of osteopontin and uses thereof |
EP3169699A4 (en) | 2014-07-18 | 2018-06-20 | The University of Washington | Cancer vaccine compositions and methods of use thereof |
NZ729206A (en) | 2014-07-23 | 2022-07-01 | Children’S Hospital & Res Center At Oakland | Factor h binding protein variants and methods of use thereof |
EP3204039B1 (en) | 2014-10-10 | 2022-06-08 | The Regents Of The University Of Michigan | Nanoemulsion compositions for preventing, suppressing or eliminating allergic and inflammatory disease |
BR112017008952A2 (en) | 2014-11-02 | 2018-01-16 | Univ North Carolina Chapel Hill | methods and compositions for recombinant dengue virus for vaccine development and diagnosis |
AR102547A1 (en) | 2014-11-07 | 2017-03-08 | Takeda Vaccines Inc | VACCINES AGAINST DISEASE OF HANDS, FEET AND MOUTH AND MANUFACTURING METHODS AND THEIR USE |
AR102548A1 (en) | 2014-11-07 | 2017-03-08 | Takeda Vaccines Inc | VACCINES AGAINST HAND, FEET AND MOUTH DISEASE AND MANUFACTURING AND USE METHODS |
BE1023004A1 (en) | 2014-12-10 | 2016-10-31 | Glaxosmithkline Biologicals Sa | PROCESSING PROCESS |
EP3242883A4 (en) | 2015-01-06 | 2018-10-17 | ImmunoVaccine Technologies Inc. | Lipid a mimics, methods of preparation, and uses thereof |
PT3244917T (en) | 2015-01-15 | 2023-05-31 | Pfizer | Immunogenic compositions for use in pneumococcal vaccines |
CA2977071A1 (en) | 2015-02-20 | 2016-08-25 | Board Of Regents, The University Of Texas System | Methods and compositions for attenuated chlamydia as vaccine and vector |
EP4226937A3 (en) | 2015-03-05 | 2023-09-27 | Northwestern University | Non-neuroinvasive viruses and uses thereof |
WO2016154010A1 (en) | 2015-03-20 | 2016-09-29 | Makidon Paul | Immunogenic compositions for use in vaccination against bordetella |
CA2980616A1 (en) | 2015-03-26 | 2016-09-29 | Gpn Vaccines Pty Ltd | Streptococcal vaccine |
US10682314B2 (en) | 2015-05-26 | 2020-06-16 | Ohio State Innovation Foundation | Nanoparticle based vaccine strategy against swine influenza virus |
WO2016193405A1 (en) | 2015-06-03 | 2016-12-08 | Affiris Ag | Il-23-p19 vaccines |
EP3313439A2 (en) | 2015-06-26 | 2018-05-02 | Seqirus UK Limited | Antigenically matched influenza vaccines |
EP3319988A1 (en) | 2015-07-07 | 2018-05-16 | Affiris AG | Vaccines for the treatment and prevention of ige mediated diseases |
KR102225282B1 (en) | 2015-07-21 | 2021-03-10 | 화이자 인코포레이티드 | Immunogenic composition comprising conjugated capsular saccharide antigen, kit comprising same, and use thereof |
EA201890630A1 (en) | 2015-09-01 | 2018-10-31 | Эйдженус Инк. | ANTIBODIES AGAINST PD-1 AND METHODS OF THEIR APPLICATION |
ES2607715B1 (en) | 2015-10-01 | 2018-01-17 | Solutex Na, Lcc | PROCESS FOR THE PREPARATION AND STABILIZATION OF EMULSIONS WITH OMEGA-3 THROUGH ISOMETRIC CRYSTAL NETWORKS OF CELLULOSE DERIVATIVES |
GB201518684D0 (en) | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Vaccine |
GB201518668D0 (en) | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Immunogenic Comosition |
EP3377098A1 (en) | 2015-11-20 | 2018-09-26 | Pfizer Inc | Immunogenic compositions for use in pneumococcal vaccines |
CN108883173B (en) | 2015-12-02 | 2022-09-06 | 阿吉纳斯公司 | Antibodies and methods of use thereof |
WO2017109698A1 (en) | 2015-12-22 | 2017-06-29 | Glaxosmithkline Biologicals Sa | Immunogenic formulation |
DK3405212T3 (en) | 2016-01-19 | 2020-08-24 | Pfizer | Cancer vaccines |
GB201603625D0 (en) | 2016-03-02 | 2016-04-13 | Glaxosmithkline Biolog Sa | Novel influenza antigens |
US20170260286A1 (en) | 2016-03-10 | 2017-09-14 | The General Hospital Corporation | Antigen-Binding Fusion Proteins with Modified HSP70 Domains |
WO2017158421A1 (en) | 2016-03-14 | 2017-09-21 | University Of Oslo | Anti-viral engineered immunoglobulins |
UA125378C2 (en) | 2016-03-14 | 2022-03-02 | Універшітетет І Осло | Engineered immunoglobulins with altered fcrn binding |
WO2017167768A1 (en) | 2016-03-28 | 2017-10-05 | Glaxosmithkline Biologicals S.A. | Novel vaccine composition |
US11173207B2 (en) | 2016-05-19 | 2021-11-16 | The Regents Of The University Of Michigan | Adjuvant compositions |
WO2017205225A2 (en) | 2016-05-21 | 2017-11-30 | Infectious Disease Research Institute | Compositions and methods for treating secondary tuberculosis and nontuberculous mycobacterium infections |
MX2018014387A (en) | 2016-05-27 | 2019-03-14 | Agenus Inc | Anti-tim-3 antibodies and methods of use thereof. |
GB201610599D0 (en) | 2016-06-17 | 2016-08-03 | Glaxosmithkline Biologicals Sa | Immunogenic Composition |
EP3471761A2 (en) | 2016-06-21 | 2019-04-24 | University Of Oslo | Hla binding vaccine moieties and uses thereof |
US11498956B2 (en) | 2016-08-23 | 2022-11-15 | Glaxosmithkline Biologicals Sa | Fusion peptides with antigens linked to short fragments of invariant chain(CD74) |
GB201614799D0 (en) | 2016-09-01 | 2016-10-19 | Glaxosmithkline Biologicals Sa | Compositions |
WO2018053294A1 (en) | 2016-09-16 | 2018-03-22 | Infectious Disease Research Institute | Vaccines comprising mycobacterium leprae polypeptides for the prevention, treatment, and diagnosis of leprosy |
US11466292B2 (en) | 2016-09-29 | 2022-10-11 | Glaxosmithkline Biologicals Sa | Compositions and methods of treatment |
TW202246349A (en) | 2016-10-11 | 2022-12-01 | 美商艾吉納斯公司 | Anti-lag-3 antibodies and methods of use thereof |
WO2018096396A1 (en) | 2016-11-22 | 2018-05-31 | University Of Oslo | Albumin variants and uses thereof |
GB201620968D0 (en) | 2016-12-09 | 2017-01-25 | Glaxosmithkline Biologicals Sa | Adenovirus polynucleotides and polypeptides |
KR20190103226A (en) | 2017-01-13 | 2019-09-04 | 아게누스 인코포레이티드 | T cell receptor that binds to NY-ESO-1 and methods of use thereof |
WO2018134693A1 (en) | 2017-01-20 | 2018-07-26 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
JP7291398B2 (en) | 2017-03-30 | 2023-06-15 | ザ ユニバーシティー オブ クイーンズランド | Chimeric molecules and uses thereof |
WO2018178265A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
WO2018178264A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
BR112019017241A2 (en) | 2017-04-13 | 2020-04-14 | Agenus Inc | anti-cd137 antibodies and methods of using them |
EP3618863B1 (en) | 2017-05-01 | 2023-07-26 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
US20200115324A1 (en) | 2017-06-11 | 2020-04-16 | Molecular Express, Inc. | Methods and compositions for substance use disorder vaccine formulations and uses thereof |
CN111315362A (en) | 2017-06-15 | 2020-06-19 | 传染病研究所 | Nanostructured lipid carriers and stable emulsions and uses thereof |
RU2020106669A (en) | 2017-07-18 | 2021-08-18 | Ин3Байо Лтд. | SYNTHETIC PROTEINS AND WAYS OF THEIR THERAPEUTIC APPLICATION |
CN110996994A (en) | 2017-08-14 | 2020-04-10 | 葛兰素史密丝克莱恩生物有限公司 | Method for enhancing immune response |
US11123415B2 (en) | 2017-08-16 | 2021-09-21 | Ohio State Innovation Foundation | Nanoparticle compositions for Salmonella vaccines |
JP7387585B2 (en) | 2017-09-04 | 2023-11-28 | アジェナス インコーポレイテッド | T-cell receptor that binds mixed lineage leukemia (MLL)-specific phosphopeptide and methods of use thereof |
US20220118076A1 (en) | 2017-09-07 | 2022-04-21 | University Of Oslo | Vaccine molecules |
EP3678699A1 (en) | 2017-09-07 | 2020-07-15 | University Of Oslo | Vaccine molecules |
US11566050B2 (en) | 2017-10-18 | 2023-01-31 | The University Of North Carolina At Chapel Hill | Methods and compositions for norovirus vaccines and diagnostics |
US11730802B2 (en) | 2017-11-03 | 2023-08-22 | Takeda Vaccines, Inc. | Zika vaccines and immunogenic compositions, and methods of using the same |
GB201721068D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B immunisation regimen and compositions |
GB201721069D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B Immunisation regimen and compositions |
GB201721576D0 (en) | 2017-12-21 | 2018-02-07 | Glaxosmithkline Biologicals Sa | Hla antigens and glycoconjugates thereof |
GB201721582D0 (en) | 2017-12-21 | 2018-02-07 | Glaxosmithkline Biologicals Sa | S aureus antigens and immunogenic compositions |
US11633471B2 (en) | 2018-03-06 | 2023-04-25 | Unm Rainforest Innovations | Compositions and methods for reducing serum triglycerides |
CN112638936A (en) | 2018-06-12 | 2021-04-09 | 葛兰素史密丝克莱恩生物有限公司 | Adenovirus polynucleotides and polypeptides |
CN112601545A (en) | 2018-08-07 | 2021-04-02 | 葛兰素史密丝克莱恩生物有限公司 | Process and vaccine |
US20210220462A1 (en) | 2018-08-23 | 2021-07-22 | Glaxosmithkline Biologicals Sa | Immunogenic proteins and compositions |
US11260119B2 (en) | 2018-08-24 | 2022-03-01 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
EP3843782A1 (en) | 2018-08-29 | 2021-07-07 | Centre Hospitalier Universitaire Vaudois (CHUV) | Ebola vaccine compositions and methods of using same |
CN111315407B (en) | 2018-09-11 | 2023-05-02 | 上海市公共卫生临床中心 | Broad-spectrum anti-influenza vaccine immunogen and application thereof |
WO2020115171A1 (en) | 2018-12-06 | 2020-06-11 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
WO2020120569A2 (en) | 2018-12-12 | 2020-06-18 | Glaxosmithkline Biologicals Sa | Modified carrier proteins for o-linked glycosylation |
CA3120922A1 (en) | 2018-12-12 | 2020-06-18 | Pfizer Inc. | Immunogenic multiple hetero-antigen polysaccharide-protein conjugates and uses thereof |
WO2020128012A1 (en) | 2018-12-21 | 2020-06-25 | Glaxosmithkline Biologicals Sa | Methods of inducing an immune response |
GB201901608D0 (en) | 2019-02-06 | 2019-03-27 | Vib Vzw | Vaccine adjuvant conjugates |
JP7239509B6 (en) | 2019-02-22 | 2023-03-28 | ファイザー・インク | Method for purifying bacterial polysaccharides |
CA3132601A1 (en) | 2019-03-05 | 2020-09-10 | Glaxosmithkline Biologicals Sa | Hepatitis b immunisation regimen and compositions |
WO2020208502A1 (en) | 2019-04-10 | 2020-10-15 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof |
EP3956666A1 (en) | 2019-04-18 | 2022-02-23 | GlaxoSmithKline Biologicals S.A. | Antigen binding proteins and assays |
MX2021014363A (en) | 2019-05-25 | 2022-02-21 | Infectious Disease Res Inst | Composition and method for spray drying an adjuvant vaccine emulsion. |
JP2022539067A (en) | 2019-06-25 | 2022-09-07 | イン3バイオ・リミテッド | Stabilized chimeric synthetic proteins and their therapeutic uses |
CA3146900A1 (en) | 2019-07-21 | 2021-01-28 | Glaxosmithkline Biologicals Sa | Therapeutic viral vaccine |
EP3770269A1 (en) | 2019-07-23 | 2021-01-27 | GlaxoSmithKline Biologicals S.A. | Quantification of bioconjugate glycosylation |
CA3148924A1 (en) | 2019-08-05 | 2021-02-11 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
US11680098B2 (en) | 2019-08-30 | 2023-06-20 | Agenus Inc. | Antibodies that specifically bind human CD96 |
EP3799884A1 (en) | 2019-10-01 | 2021-04-07 | GlaxoSmithKline Biologicals S.A. | Immunogenic compositions |
EP3808765A1 (en) | 2019-10-14 | 2021-04-21 | ETH Zurich | Cell line for tcr discovery and engineering and methods of use thereof |
EP4051696A1 (en) | 2019-11-01 | 2022-09-07 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
WO2021097347A1 (en) | 2019-11-15 | 2021-05-20 | Infectious Disease Research Institute | Rig-i agonist and adjuvant formulation for tumor treatment |
NL2030835B1 (en) | 2020-01-24 | 2022-12-29 | Aim Immunotech Inc | Methods, compositions, and vaccinces for treating a virus infection |
WO2021160887A1 (en) | 2020-02-14 | 2021-08-19 | Immunor As | Corona virus vaccine |
KR20220144393A (en) | 2020-02-21 | 2022-10-26 | 화이자 인코포레이티드 | sugar purification |
MX2022010350A (en) | 2020-02-23 | 2022-09-19 | Pfizer | Compositions and methods thereof. |
WO2021205077A1 (en) | 2020-04-09 | 2021-10-14 | Finncure Oy | Mimetic nanoparticles for preventing the spreading and lowering the infection rate of novel coronaviruses |
US20230234992A1 (en) | 2020-06-05 | 2023-07-27 | Glaxosmithkline Biologicals Sa | Modified betacoronavirus spike proteins |
EP4171629A1 (en) | 2020-06-29 | 2023-05-03 | GlaxoSmithKline Biologicals S.A. | Adjuvants |
WO2022038157A1 (en) | 2020-08-17 | 2022-02-24 | Universität Basel | Lfa-1 signalling mediator for use in cancer therapy |
EP4200317A1 (en) | 2020-08-24 | 2023-06-28 | Sanofi Pasteur Inc. | Covid-19 vaccines with tocopherol-containing squalene emulsion adjuvants |
US11225508B1 (en) | 2020-09-23 | 2022-01-18 | The University Of North Carolina At Chapel Hill | Mouse-adapted SARS-CoV-2 viruses and methods of use thereof |
CN113999315A (en) | 2020-10-23 | 2022-02-01 | 江苏省疾病预防控制中心(江苏省公共卫生研究院) | Fusion protein and application thereof |
JP2023546615A (en) | 2020-10-27 | 2023-11-06 | ファイザー・インク | E. coli composition and method thereof |
WO2022097010A1 (en) | 2020-11-04 | 2022-05-12 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
WO2022101745A2 (en) | 2020-11-10 | 2022-05-19 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
US20220202923A1 (en) | 2020-12-23 | 2022-06-30 | Pfizer Inc. | E. coli fimh mutants and uses thereof |
WO2022147373A1 (en) | 2020-12-31 | 2022-07-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibody-guided pcsk9-mimicking immunogens lacking 9-residue sequence overlap with human proteins |
US20220226465A1 (en) | 2021-01-18 | 2022-07-21 | ConserV Bioscience | Coronavirus Immunogenic Compositions, Methods and Uses Thereof |
EP4032547A1 (en) | 2021-01-20 | 2022-07-27 | GlaxoSmithKline Biologicals S.A. | Hsv1 fce derived fragements for the treatment of hsv |
JP2024507828A (en) | 2021-02-19 | 2024-02-21 | サノフィ パスツール インコーポレイテッド | Group B meningococcal recombinant vaccine |
EP4294433A1 (en) | 2021-02-22 | 2023-12-27 | GlaxoSmithKline Biologicals SA | Immunogenic composition, use and methods |
WO2022200582A1 (en) | 2021-03-26 | 2022-09-29 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
US20220387576A1 (en) | 2021-05-28 | 2022-12-08 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
PE20240090A1 (en) | 2021-05-28 | 2024-01-16 | Pfizer | IMMUNOGENIC COMPOSITIONS COMPRISING CONJUGATED CAPSULAR SACCHARIDE ANTIGENS AND THEIR USES |
WO2023274860A1 (en) | 2021-06-28 | 2023-01-05 | Glaxosmithkline Biologicals Sa | Novel influenza antigens |
WO2023020994A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023020992A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023020993A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023061993A1 (en) | 2021-10-13 | 2023-04-20 | Glaxosmithkline Biologicals Sa | Polypeptides |
WO2023092090A1 (en) | 2021-11-18 | 2023-05-25 | Matrivax, Inc. | Immunogenic fusion protein compositions and methods of use thereof |
WO2023135515A1 (en) | 2022-01-13 | 2023-07-20 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2023161817A1 (en) | 2022-02-25 | 2023-08-31 | Pfizer Inc. | Methods for incorporating azido groups in bacterial capsular polysaccharides |
WO2023218322A1 (en) | 2022-05-11 | 2023-11-16 | Pfizer Inc. | Process for producing of vaccine formulations with preservatives |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988009336A1 (en) * | 1987-05-29 | 1988-12-01 | Cambridge Bioscience Corporation | Saponin adjuvant |
EP0382271A1 (en) * | 1989-02-04 | 1990-08-16 | Akzo Nobel N.V. | Tocols as adjuvant in vaccine |
EP0399843A2 (en) * | 1989-05-25 | 1990-11-28 | Chiron Corporation | Adjuvant formulation comprising a submicron oil droplet emulsion |
WO1992016556A1 (en) * | 1991-03-21 | 1992-10-01 | Smithkline Beecham Biologicals (S.A.) | Derivatives opf gp160 and vaccines based on gp160 or a derivative thereof, containing an adjuvant |
WO1994000153A1 (en) * | 1992-06-25 | 1994-01-06 | Smithkline Beecham Biologicals (S.A.) | Vaccine composition containing adjuvants |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4606918A (en) * | 1983-08-22 | 1986-08-19 | Syntex (U.S.A.) Inc. | Polyoxypropylene-polyoxyethylene block polymer based adjuvants |
US5554372A (en) * | 1986-09-22 | 1996-09-10 | Emory University | Methods and vaccines comprising surface-active copolymers |
US5057540A (en) * | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
AU626271B2 (en) * | 1987-11-03 | 1992-07-30 | Syntex (U.S.A.) Inc. | Vaccine adjuvant |
US4912094B1 (en) * | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
NZ238731A (en) * | 1990-06-27 | 1996-02-27 | Univ Emory | Vaccine adjuvant compositions comprising ethyleneoxy-propyleneoxy-ethyleneoxy block copolymer or a non-toxic lipopolysaccharide |
US5709879A (en) * | 1990-06-29 | 1998-01-20 | Chiron Corporation | Vaccine compositions containing liposomes |
DK0489153T3 (en) * | 1990-06-29 | 2000-01-24 | Chiron Corp | Vaccine preparations containing liposomes |
KR100194079B1 (en) * | 1990-09-28 | 1999-06-15 | 장 스테판느 | Pharmaceutical composition for preventing or treating HIV infection and method for preparing same |
GB9105992D0 (en) * | 1991-03-21 | 1991-05-08 | Smithkline Beecham Biolog | Vaccine |
DK0596032T4 (en) | 1991-07-25 | 2004-07-26 | Idec Pharma Corp | Induction of cytotoxic T lymphocyte responses |
US6620414B2 (en) | 1992-03-27 | 2003-09-16 | Smithkline Beecham Biologicals (S.A.) | Hepatitis vaccines containing 3-0-deacylated monophoshoryl lipid A |
DE69405551T3 (en) * | 1993-03-23 | 2005-10-20 | Smithkline Beecham Biologicals S.A. | 3-0-DEAZYLATED MONOPHOSPHORYL LIPID A-CONTAINING VACCINE COMPOSITIONS |
CA2163550A1 (en) * | 1993-05-25 | 1994-12-08 | Gerald E. Hancock | Adjuvants for vaccines against respiratory syncytial virus |
GB9326253D0 (en) * | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
GB9718901D0 (en) | 1997-09-05 | 1997-11-12 | Smithkline Beecham Biolog | Vaccine |
EP1009382B1 (en) | 1997-09-05 | 2003-06-18 | GlaxoSmithKline Biologicals S.A. | Oil in water emulsions containing saponins |
-
1993
- 1993-12-23 GB GB939326253A patent/GB9326253D0/en active Pending
-
1994
- 1994-12-15 WO PCT/EP1994/004227 patent/WO1995017209A1/en active Application Filing
- 1994-12-15 AU AU13164/95A patent/AU1316495A/en not_active Abandoned
- 1994-12-20 NZ NZ277802A patent/NZ277802A/en not_active IP Right Cessation
- 1994-12-20 ES ES98201308T patent/ES2219837T3/en not_active Expired - Lifetime
- 1994-12-20 NZ NZ329661A patent/NZ329661A/en not_active IP Right Cessation
- 1994-12-20 PT PT03075344T patent/PT1327451E/en unknown
- 1994-12-20 PT PT98201308T patent/PT868918E/en unknown
- 1994-12-20 DK DK95904511T patent/DK0735898T3/en active
- 1994-12-20 SG SG1996008446A patent/SG49257A1/en unknown
- 1994-12-20 SG SG1998004593A patent/SG73578A1/en unknown
- 1994-12-20 DK DK03075344T patent/DK1327451T3/en active
- 1994-12-20 WO PCT/EP1994/004246 patent/WO1995017210A1/en active IP Right Grant
- 1994-12-20 DK DK98201308T patent/DK0868918T3/en active
- 1994-12-20 EP EP07103910A patent/EP1792628A1/en not_active Withdrawn
- 1994-12-20 US US08/663,289 patent/US6146632A/en not_active Expired - Lifetime
- 1994-12-20 SI SI9430467T patent/SI0868918T1/en unknown
- 1994-12-20 ES ES95904511T patent/ES2129801T3/en not_active Expired - Lifetime
- 1994-12-20 AT AT95904511T patent/ATE177322T1/en active
- 1994-12-20 DE DE122008000055C patent/DE122008000055I1/en active Pending
- 1994-12-20 KR KR1019960703308A patent/KR100350965B1/en not_active IP Right Cessation
- 1994-12-20 AT AT03075344T patent/ATE359818T1/en active
- 1994-12-20 SI SI9430231T patent/SI0735898T1/en unknown
- 1994-12-20 DE DE69433750T patent/DE69433750T2/en not_active Expired - Lifetime
- 1994-12-20 DE DE122008000054C patent/DE122008000054I1/en active Pending
- 1994-12-20 CA CA2179779A patent/CA2179779C/en not_active Expired - Lifetime
- 1994-12-20 AT AT98201308T patent/ATE265228T1/en active
- 1994-12-20 EP EP03075344A patent/EP1327451B1/en not_active Expired - Lifetime
- 1994-12-20 JP JP51718795A patent/JP4125781B2/en not_active Expired - Lifetime
- 1994-12-20 CN CN94194554A patent/CN1086589C/en not_active Expired - Fee Related
- 1994-12-20 SI SI9430483T patent/SI1327451T1/en unknown
- 1994-12-20 ES ES03075344T patent/ES2285036T3/en not_active Expired - Lifetime
- 1994-12-20 EP EP95904511A patent/EP0735898B1/en not_active Expired - Lifetime
- 1994-12-20 DE DE69434956T patent/DE69434956T2/en not_active Expired - Lifetime
- 1994-12-20 EP EP98201308A patent/EP0868918B1/en not_active Expired - Lifetime
- 1994-12-20 DE DE69417063T patent/DE69417063T2/en not_active Expired - Lifetime
- 1994-12-21 ZA ZA9410176A patent/ZA9410176B/en unknown
-
1998
- 1998-05-22 AU AU68032/98A patent/AU705519B2/en not_active Ceased
- 1998-05-22 AU AU68031/98A patent/AU705521B2/en not_active Ceased
- 1998-12-15 HK HK03108906A patent/HK1057991A1/en not_active IP Right Cessation
- 1998-12-15 HK HK98113482A patent/HK1012243A1/en not_active IP Right Cessation
- 1998-12-15 HK HK00100405A patent/HK1021504A1/en not_active IP Right Cessation
-
1999
- 1999-03-19 GR GR990400835T patent/GR3029750T3/en unknown
-
2000
- 2000-02-24 US US09/513,255 patent/US6623739B1/en not_active Expired - Fee Related
-
2003
- 2003-09-03 US US10/654,279 patent/US7029678B2/en not_active Expired - Fee Related
-
2005
- 2005-08-10 US US11/200,601 patent/US7169391B2/en not_active Expired - Fee Related
- 2005-09-16 CY CY0500051A patent/CY2530B1/en unknown
-
2006
- 2006-02-23 JP JP2006046982A patent/JP4126067B2/en not_active Expired - Fee Related
-
2007
- 2007-01-12 US US11/622,582 patent/US7510698B2/en not_active Expired - Fee Related
- 2007-06-21 JP JP2007163766A patent/JP4126079B2/en not_active Expired - Lifetime
-
2008
- 2008-10-15 LU LU91485C patent/LU91485I2/en unknown
- 2008-10-15 LU LU91486C patent/LU91486I2/en unknown
- 2008-10-17 CY CY0800019A patent/CY2593B2/en unknown
- 2008-10-22 NL NL300362C patent/NL300362I1/en unknown
- 2008-10-22 NL NL300363C patent/NL300363I1/en unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988009336A1 (en) * | 1987-05-29 | 1988-12-01 | Cambridge Bioscience Corporation | Saponin adjuvant |
EP0382271A1 (en) * | 1989-02-04 | 1990-08-16 | Akzo Nobel N.V. | Tocols as adjuvant in vaccine |
EP0399843A2 (en) * | 1989-05-25 | 1990-11-28 | Chiron Corporation | Adjuvant formulation comprising a submicron oil droplet emulsion |
WO1992016556A1 (en) * | 1991-03-21 | 1992-10-01 | Smithkline Beecham Biologicals (S.A.) | Derivatives opf gp160 and vaccines based on gp160 or a derivative thereof, containing an adjuvant |
WO1994000153A1 (en) * | 1992-06-25 | 1994-01-06 | Smithkline Beecham Biologicals (S.A.) | Vaccine composition containing adjuvants |
Cited By (121)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US7510698B2 (en) | 1993-12-23 | 2009-03-31 | Glaxosmithkline Biologicals Sa | Vaccines |
US6146632A (en) * | 1993-12-23 | 2000-11-14 | Smithkline Beecham Biologicals S.A. | Vaccines |
EP1327451A1 (en) * | 1993-12-23 | 2003-07-16 | GlaxoSmithKline Biologicals S.A. | Adjuvants for vaccines |
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WO1997001640A3 (en) * | 1995-06-29 | 1997-05-15 | Smithkline Beecham Biolog | Vaccines against hepatitis c |
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US7718178B2 (en) | 1997-04-05 | 2010-05-18 | Allergy Therapeutics Limited | Allergen formulation |
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US9463198B2 (en) | 2013-06-04 | 2016-10-11 | Infectious Disease Research Institute | Compositions and methods for reducing or preventing metastasis |
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