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Stabilised proteins for immunising against Staphylococcus aureus

An immunogenic, carrier protein technology, applied in peptide/protein components, vaccines, organic chemistry, etc., which can solve the problems of complex vaccine production, requirements affecting quality and regulatory approval, and unstable antigens.

Inactive Publication Date: 2015-06-24
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Antigenic instability is undesirable because (1) this prevents vaccines from being stored for extended periods of time prior to administration, and (2) inconsistencies between vaccine batches can affect quality and regulatory approval requirements
Furthermore, the production of vaccines containing these unstable antigens can be complicated and involve multiple purification steps

Method used

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  • Stabilised proteins for immunising against Staphylococcus aureus
  • Stabilised proteins for immunising against Staphylococcus aureus
  • Stabilised proteins for immunising against Staphylococcus aureus

Examples

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Embodiment Construction

[0252] Immunogenicity studies in mice

[0253]The immunogenicity of cysteine-containing (Cys(+)) S. aureus antigens was compared to the corresponding cysteine-deficient (Cys(-)) variants. Five-week-old CD1 mice were immunized intraperitoneally with 14-day interval prime-boost injections of purified recombinant protein adsorbed to aluminum hydroxide adjuvant (Aluminum, 2 mg / ml). Mice were divided into 3 groups: (1) "combined Cys(+)Lyo format": with quadrivalent vaccine containing EsxAB-Cys(+), Sta006Cys(+), Sta011Cys(+), HlaH35L and aluminum hydroxide adjuvant Immunized mice; (2) "combined Cys(-)": mice immunized with quadrivalent vaccine containing EsxAB Cys(-), Sta006Cys(-), Sta011Cys(-), HlaH35L and aluminum hydroxide adjuvant; and (3) "Aluminum 2 mg / ml+NaCl": control mice receiving equal amounts of PBS and aluminum hydroxide adjuvant. Animals were bled immediately before the first immunization and 23 days later, and IgG antibodies against purified proteins were detected i...

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Abstract

Elimination of disulphide bond formation ofcysteine-containing S.aureus antigens enhances antigen stability. The invention provides a composition comprising variant forms of cysteine-containing S.aureus antigen with a point mutation that replaces, deletes or modifies the cysteine residue.

Description

[0001] This application claims the benefit of US Provisional Application 61 / 695,782, filed August 31, 2012, the entire contents of which are incorporated herein by reference for all purposes. technical field [0002] The present invention relates to immunogenic compositions comprising antigens derived from Staphylococcus aureus and their use in immunization. Background technique [0003] Staphylococcus aureus is a Gram-positive coccus and is a major cause of bloodstream, lower respiratory tract and skin and other soft tissue infections. It causes illnesses ranging from mild skin infections to fatal illnesses including pneumonia and sepsis, and causes more annual deaths in the United States associated with S. aureus than any other infectious disease, including HIV / AIDS. [0004] There are currently no approved vaccines against S. aureus. In a phase III clinical trial in 2005, the vaccine StaphVAX based on a mixture of surface polysaccharides from bacteria types 5 and 8 was c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61K39/085C07K1/113C07K14/315
CPCC07K14/3156A61K39/085A61K39/39A61K2039/55511A61K2039/70
Inventor F·巴格诺利S·布法力S·恰内蒂A·考斯洛维G·格兰迪M·尼森M·帕劳罗S·萨维诺M·索特朱
Owner NOVARTIS AG
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