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Pneumococcal surface protein C (PspC), epitopic regions and strain selection thereof, and uses therefor

a technology of surface protein and pneumococcal, applied in the field of pneumococcal surface protein c (pspc), can solve the problems of difficult approach, neonates and young children failing to make adequate immune responses to most, and achieving the effect of enhancing immunogenicity and enhancing immunogenicity

Inactive Publication Date: 2001-08-23
UAB RES FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0034] A polypeptide comprising at least a fragment or epitope of PspC, e.g., an epitopic region of PspC or PspC, can be a fusion protein; for instance, fused to a protein which enhances immunogenicity, such as a Cholera Toxin, e.g., Cholera Toxin B (CTB).

Problems solved by technology

It is also a leading cause of morbidity in young children.
However, neonates and young children fail to make adequate immune response against most capsular polysaccharide antigens and can have repeated infections involving the same capsular serotype.
This approach may be difficult, because the twenty-three polysaccharides included in the presently-available vaccine are not all adequately immunogenic, even in adults.
However, the efficacy of the vaccine has been controversial, and at times, the justification for the recommended use of the vaccine questioned.
It has been speculated that the efficacy of this vaccine is negatively affected by having to combine 23 different antigens.
Having a large number of antigens combined in a single formulation may negatively affect the antibody responses to individual types within this mixture because of antigenic competition.

Method used

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  • Pneumococcal surface protein C (PspC), epitopic regions and strain selection thereof, and uses therefor
  • Pneumococcal surface protein C (PspC), epitopic regions and strain selection thereof, and uses therefor
  • Pneumococcal surface protein C (PspC), epitopic regions and strain selection thereof, and uses therefor

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AND RESULTS

Materials and methods

[0098] Bacterial strains, plasmids, and recombinant DNA techniques

[0099] Chromosomal DNA from S. pneumoniae EF6796, a serotype 6A clinical isolate (Salser et al. 1993) and D39, a serotype 2 isolate, was isolated using a cesium chloride gradient procedure. The HindIII-EcoRI fragment of EF6796 and D39 was cloned in a modified pZero vector (Invitrogen, San Diego, Calif.) in which the Zeocin-resistance cassette was replaced by a kanamycin cassette, kindly provided by Randall Harris. Recombinant plasmids were electroporated into Escherichia coli TOP10F' cells [F'{lacI.sup.qTet.sup.R} mcrA_(mrr-hsdRMS-mcrBC) f80lacZ_M15_lacX74 deoR recA1 araD139_(ara-leu)7697 galU galK rpsL endA1 nupG] (Invitrogen). DNA was purified from agarose using Gene Clean (Bio101, Inc., Vista, Calif.).

[0100] Chromosomal DNA used for PCR was isolated using a chloroform-isoamyl alcohol procedure. Oligonucleotide primers, ABW13 (5' CGACGAATAGCTGAAGAGG 3') (SEQ ID NO: ) and SKH2 (5' CATA...

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Abstract

Disclosed and claimed are: epitopic regions of Pneumococcal Surface Protein C or "PspC", different clades of PspC, isolated and / or purified nucleic acid molecules such as DNA encoding a fragment or portion of PspC such as an epitopic region of PspC or at least one epitope of PspC, uses for such nucleic acid molecules, e.g., to detect the presence of PspC or of S. pneumoniae by detecting a nucleic acid molecule therefor in a sample such as by amplification and / or a polymerase chain reaction, vectors or plasmids which contain and / or express such nucleic acid molecles, e.g., in vitro or in vivo, immunological, immunogenic or vaccine compositions including at least one PspC and / or a portion thereof (such as at least one epitopic region of at least one PspC and / or at least one polypeptide encoding at least one epitope of at least one PspC), either alone or in further combination with at least one second pneumococcal antigen, such as at least one different PspC and / or a fragment thereof and / or at least one PspA and / or at least one epitopic region of at least one PspA and / or at least one polypeptide including at least one epitope of PspA. PspC or a fragment thereof, and thus a composition including PspC or a fragment thereof, can be administered by the same routes, and in approximately the same amounts, as PspA. Thus, the invention further provides methods for administering PspC or a fragment thereof, as well as uses of PspC or a fragment thereof to formulate such compositions.

Description

[0001] al., "Truncated PspA . . . ," U.S. application Ser. No. 08 / 214,222, filed Mar. 17, 1994 (now U.S. Pat. No. 5,804,193); Briles et al. U.S. application Ser. No. 08 / 468,985 (allowed); Briles et al., "Immunoassay Comprising a Truncated Pneumococcal Surface Protein A (PspA)," U.S. Pat. No. 5,871,943; U.S. applications Ser. Nos. 08 / 226,844, filed May 29, 1992, 08 / 093,907, filed Jul. 5, 1994.and 07 / 889,918, filed Jul. 5, 1994; PCT / US93 / 05191; and Briles et al., WO 92 / 1448.[0002] Each of these applications and patents, as well as each document or reference cited in each of these applications and patents (including during the prosecution of each issued patent) and PCT and foreign applications or patents corresponding to and / or claiming priority from any of the foregoing applications and patents, is hereby expressly incorporated herein by reference. Documents or references are also cited in the following text, either in a Reference List before the claims, or in the text itself; and, ea...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00A61K39/02C07H21/04C07K14/31C07K14/315C12N1/21C12N15/74C12Q1/68
CPCA61K39/00A61K2039/51C07K14/3156
Inventor BRILES, DAVID E.HOLLINGSHEAD, SUSAN K.BROOKS-WALTER, ALEXIS
Owner UAB RES FOUND
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