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Vaccine

a streptococcus pneumoniae and vaccine technology, applied in the field of vaccines, can solve the problems of inadequate th-cells available to provide the necessary help, immunological effects, and diminishing the immune respons

Inactive Publication Date: 2009-01-15
GLAXOSMITHKLINE BIOLOGICALS SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there can be issues with repeat administration of polysaccharide-protein conjugates, or the combination of polysaccharide-protein conjugates to form multivalent vaccines.
If the B-cells to the carrier protein predominate, there are not enough Th-cells available to provide the necessary help for the B-cells specific to the polysaccharide.
However, the observed immunological effects have been inconsistent, with the total amount of carrier protein in some instances increasing the immune response, and in other cases diminishing the immune response.
Hence there remain technical difficulties in combining multiple polysaccharide conjugates into a single, efficacious, vaccine formulation.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Expression of Protein D

[0177]Haemophilus influenzae Protein D

Genetic Construction for Protein D Expression

[0178]Starting Materials

The Protein D Encoding DNA

[0179]Protein D is highly conserved among H. influenzae of all serotypes and non-typeable strains. The vector pHIC348 containing the DNA sequence encoding the entire protein D gene has been obtained from Dr. A. Forsgren, Department of Medical Microbiology, University of Lund, Malmö General Hospital, Malmö, Sweden. The DNA sequence of protein D has been published by Janson et al. (1991) Infect. Immun. 59: 119-125.

The Expression Vector pMG1

[0180]The expression vector pMG1 is a derivative of pBR322 (Gross et al., 1985) in which bacteriophage λ derived control elements for transcription and translation of foreign inserted genes were introduced (Shatzman et al., 1983). In addition, the Ampicillin resistance gene was exchanged with the Kanamycin resistance gene.

The E. coli strain AR58

[0181]The E. coli strain AR58 was generated by trans...

example 1b

Expression of PhtD

[0200]The PhtD protein is a member of the pneumococcal histidine-triad (Pht) protein family characterized by the presence of histidine-triads (HXXHXH motif). PhtD is a 838 aa-molecule and carries 5 histidine triads (see MedImmune WO00 / 37105 SEQ ID NO: 4 for amino acid sequence and SEQ ID NO: 5 for DNA sequence). PhtD also contains a proline-rich region in the middle (amino acid position 348-380). PhtD has a 20 aa-N-terminal signal sequence with a LXXC motif.

Genetic Construct

[0201]The gene sequence of the mature MedImmune PhtD protein (from aa 21 to aa 838) was transferred recombinantly to E. coli using the in-house pTCMP14 vector carrying the pλ promoter. The E. coli host strain is AR58, which carries the cI857 thermosensitive repressor, allowing heat-induction of the promotor.

[0202]Polymerase chain reaction was realized to amplify the phtD gene from a MedImmune plasmid (carrying the phtD gene from Streptococcus pneumoniae strain Norway 4 (serotype 4)—SEQ ID NO: 5 ...

example 1c

Expression of Pneumolysin

[0212]Pneumococcal pneumolysin was prepared and detoxified as described in WO2004 / 081515 and WO2006 / 032499.

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Abstract

The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, an immunogenic composition for infants is provided comprising a multivalent Streptococcus pneumoniae vaccine comprising 2 or more capsular saccharide conjugates from different serotypes, wherein the composition comprises a serotype 22F saccharide conjugate. Such a vaccine may be used in infant populations to reduce the incidence of elderly pneumococcal disease such as exacerbations of COPD and / or IPD.

Description

FIELD OF THE INVENTION[0001]The present invention relates to an improved Streptococcus pneumoniae vaccine.BACKGROUND OF THE INVENTION[0002]Children less than 2 years of age do not mount an immune response to most polysaccharide vaccines, so it has been necessary to render the polysaccharides immunogenic by chemical conjugation to a protein carrier. Coupling the polysaccharide, a T-independent antigen, to a protein, a T-dependent antigen, confers upon the polysaccharide the properties of T dependency including isotype switching, affinity maturation, and memory induction.[0003]However, there can be issues with repeat administration of polysaccharide-protein conjugates, or the combination of polysaccharide-protein conjugates to form multivalent vaccines. For example, it has been reported that a Haemophilus influenzae type b polysaccharide (PRP) vaccine using tetanus toxoid (TT) as the protein carrier was tested in a dosage-range with simultaneous immunization with (free) TT and a pneum...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/09A61P31/04
CPCA61K39/092A61K2039/6068A61K2039/6037A61K2039/545A61K2039/55A61K2039/555A61K2039/62A61K47/6415A61K47/646A61K2039/627A61K2039/70A61P11/00A61P25/00A61P27/02A61P27/14A61P27/16A61P29/00A61P31/00A61P31/04A61P37/00A61P37/04A61P43/00A61P7/00A61K39/145A61K39/12A61K39/385A61K47/61A61K2039/6031A61K2039/6087Y02A50/30A61K2039/55566A61K2039/575
Inventor BIEMANS, RALPH LEONGARCON, NATHALIE MARIE-JOSEPHEHERMAND, PHILIPPE VINCENTPOOLMAN, JANVAN MECHELEN, MARCELLE PAULETTE
Owner GLAXOSMITHKLINE BIOLOGICALS SA
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