Stabilised proteins for immunising against staphylococcus aureus

一种蛋白、免疫原性的技术，应用在抗细菌药、含有效成分的医用配制品、过敏性疾病等方向，能够解决疫苗不一致性影响、抗原不稳定、疫苗生产复杂等问题

Inactive Publication Date: 2015-05-13
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 in vaccines from batch to batch can affect quality and regulatory agency 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

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0200] heat denaturation test

[0201] The Sta006Cys(+) antigen used in the experiments described below is represented as SEQ ID NO:3 and the Sta006Cys(-) antigen is represented as SEQ ID NO:6. Both antigens are recombinant proteins purified from E. coli.

[0202] The thermostability of Sta006 cysteine-containing Cys(+) antigen and Sta006 cysteine-deficient Cys(-) antigen was compared by differential scanning fluorescence assay (DSF). Antigen-containing samples (10 μΜ in PBS) were heated under controlled conditions in a Strategen Mx3000p real-time PCR instrument at a temperature ramp rate of 1 °C / min. The dye SyproOrange 5x was used and the change in fluorescence was monitored. The tests were carried out in the temperature range of 10-100°C.

[0203] figure 1 Melting curves for the tested antigens are reported. It shows that the peak of Cys(-) antigen is slightly shifted to the top and left compared to Cys(+) antigen. Melting temperature (Tm) was determined by fitting the ...

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Abstract

Elimination of disulphide bond formation of cysteine-containing S.aureus antigens enhances antigen stability. The invention provides 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 / 695,723, 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 a variety of illnesses ranging from mild skin infections to fatal illnesses including pneumonia and sepsis, and the annual death rate associated with S. aureus in the United States exceeds that of 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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/085
CPCA61K39/085A61K2039/55505A61P31/04A61P37/04C07K14/31
Inventor F·巴格诺利F·法路基G·格兰迪M·玛丽安尼M·尼森M·帕劳罗S·萨维诺
Owner NOVARTIS AG
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