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- Document 0104
- DOCN M9620104
- TI Construction and characterization of a Salmonella typhi-based human
- immunodeficiency virus type 1 vector vaccine.
- DT 9602
- AU Fouts TR; Lewis GK; Hone DM; Department of Geographic Medicine, School
- of Medicine, University; of Maryland at Baltimore 21201, USA.
- SO Vaccine. 1995 Apr;13(6):561-9. Unique Identifier : AIDSLINE MED/96065464
- AB Since the human immunodeficiency virus type 1 (HIV-1) is transmitted
- either parenterally or sexually, both systemic and mucosal immune
- responses might be required to provide protective immunity. One option
- is to express HIV proteins in attenuated Salmonella vectors that elicit
- immune responses in both compartments. The first step to constructing
- such a strain was achieved by integrating a gene expression cassette
- encoding recombinant HIV-1 gp120 (rgp120) into the aroC locus of an
- attenuated vaccine strain of S. typhi. This rgp120 expression cassette
- utilizes the strong constitutive promoter, P1pp/lacUV5, and produces
- rgp120 to 0.05-01% of the total bacterial cell protein. Immunoblot
- analysis shows that the S. typhi strains containing the integrated
- cassette express a protein that is both recognized by anti-gp120
- monoclonal antibodies (mAbs) and is the appropriate size for
- nonglycosylated full-length gp120 (52 kDa). Immunoblot analysis also
- demonstrates that the recombinant S. typhi strains express the rgp120 as
- monomers and multimers found predominantly in the insoluble fraction of
- the bacteria. Antigen-capture ELISA, using antibodies specific for
- continuous epitopes on gp120, revealed that the exposure of these
- epitopes on S. typhi-expressed rgp120 differs from exposure of these
- epitopes on baculovirus-expressed rgp120 that binds CD4. Epitopes in the
- first conserved region (109-113) and the third conserved/fourth variable
- regions (376-380, 382-384, 395-400) are more surface-exposed, while one
- epitope in the third variable region (313-324) is more buried relative
- to the corresponding epitopes of baculovirus expressed gp120. Antibodies
- recognizing discontinuous epitopes of the CD4 binding domain do not
- react with the S. typhi expressed rgp120.(ABSTRACT TRUNCATED AT 250
- WORDS)
- DE AIDS Vaccines/*GENETICS/IMMUNOLOGY B-Lymphocytes/IMMUNOLOGY Base
- Sequence Cloning, Molecular Comparative Study Epitopes/IMMUNOLOGY
- Genetic Vectors HIV Envelope Protein gp120/*GENETICS/*IMMUNOLOGY
- HIV-1/*IMMUNOLOGY Molecular Sequence Data Mutagenesis, Insertional
- Recombinant Proteins/GENETICS/IMMUNOLOGY Salmonella
- typhi/*GENETICS/METABOLISM Support, Non-U.S. Gov't Support, U.S.
- Gov't, P.H.S. Vaccines, Attenuated/GENETICS/IMMUNOLOGY JOURNAL ARTICLE
-
- SOURCE: National Library of Medicine. NOTICE: This material may be
- protected by Copyright Law (Title 17, U.S.Code).
-
-