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Induction of an immune response against streptococcus pneumoniae polysaccharides

A Streptococcus pneumoniae, polysaccharide technology, applied in bacterial peptides, antibacterial drugs, bacterial antigen components, etc.

Inactive Publication Date: 2007-07-04
PHARMEXA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This 23-valent pneumococcal polysaccharide vaccine has been made available by many manufacturers worldwide and is effective in individuals 2 years of age or older: however, because they elicit a T-cell-independent response, these vaccines are Ineffective in children younger than 2 years (EskolaJ, Anttila M. 1999, 18:543-51)

Method used

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  • Induction of an immune response against streptococcus pneumoniae polysaccharides
  • Induction of an immune response against streptococcus pneumoniae polysaccharides
  • Induction of an immune response against streptococcus pneumoniae polysaccharides

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Experimental program
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preparation example Construction

[0237] 3. Preparation of Conjugates

[0238] Conjugation of the desired polysaccharide to a polypeptide comprising the pan DR peptide sequence can be accomplished by a number of methods. Polysaccharides can be attached to the polysaccharides of the invention by enzymatic or chemical reactions. A wide range of ligation strategies are described, for example, in Hermanson, BIOCONJUGATE TECHNIQUES (Academic Press, 1996); Lockhart, "Conjugate Vaccines," Expert Rev. Vaccines 2(5):633-648 (2003). Ionic interactions are possible via the termini or via the ε-amino groups of lysines. Hydrogen bonding between residue side groups and epitopes is also possible.

[0239] In some embodiments, the polysaccharide / pan DR binding peptide conjugates are linked by a spacer or linker. Alternatively, the polysaccharide can be directly attached to the pan DR binding peptide without a linker.

[0240] The spacers or linkers may consist of neutral molecules, such as aliphatic carbon chains, amino a...

Embodiment

[0278] The following examples are offered by way of illustration and not limitation.

[0279] An experimental carbohydrate-conjugate vaccine was produced consisting of a 13 amino acid universal PanHLA-DR epitope and S. pneumoniae envelope polysaccharides from serotypes 14, 6B and 9V. Simple carbodiimide-mediated condensation chemistry was used to conjugate the pan DR-bound synthetic peptides to 3 chemically distinct capsular polysaccharides in a 1:1 molar ratio. The immunogenicity of the pan DR-binding peptide component of the conjugate vaccine was demonstrated by inducing a pan DR-binding peptide-specific CD4+ helper T cell (HTL) response after immunization of C57BL / 6 mice. Apply complete Freund's adjuvant and aluminum glue Al(OH) 3 formulation, induces high-titer antibody responses specific to Streptococcus pneumoniae serotypes 14, 6B and 9V. The effect of the HTL, or vector, pan DR binding synthetic peptide was only evident when using the pan DR binding peptide-polysaccha...

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Abstract

The present invention provides conjugates of pan DR binding peptides with Streptococcus pneumoniae polysaccharides, and methods of preventing and treating diseases associated with Streptococcus pneumoniae infection with such conjugates.

Description

Background of the invention [0001] It is generally known that the nature of the immune response elicited against a particular vaccine antigen is important to the overall efficacy of the vaccine. In the case of carbohydrate antigens, a number of methods have been studied in an attempt to enhance their immunogenicity, including chemical modification (Jennings, et al. In Towards Better Carbohydrate Vaccines, Bell and Torrigiani (eds) pp. 11-17 , J.Wiley & Sons, London, 1987), administered with an adjuvant, non-covalently complexed with protein, covalently attached to an immunogenic protein carrier (Schneerson, et al. In Towards Better Carbohydrate Vaccines, as previously described, pp. 307-327), and replace carbohydrate epitopes with protein replicas that are de novo synthesized peptides (so-called mimitopes, Geyson, et al. In Towards Better Carbohydrate Vaccines, e.g. supra, pp. 103-118) or antiidiotypic antibodies (Soederstroem in Towards Better Carbohydrate Vaccines, supra, p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/09C07K4/04A61K31/715A61K47/48
CPCA61K47/4833A61K2039/627A61K31/715A61K39/09A61K47/646A61P31/04
Inventor J·L·亚历山大A·塞特M·J·纽曼
Owner PHARMEXA
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