AEGiS-13IAC: Highly immunogenic live recombinant BCG and vaccinia virus DIs strain both of which express whole gab antigen of HIV-1.

13th International AIDS Conference


Durban, South Africa - July 9-July 14, 2000

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Highly immunogenic live recombinant BCG and vaccinia virus DIs strain both of which express whole gab antigen of HIV-1.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA293)

Matsuo K, Ohsu T, Kanekiyo M, Hamatake M, Hamano T, Honda M;;; K. Matsuo, JST AIDS Vaccine Project, NIH, DMSC, Ministry of Public Health, Tivanond Road, Nonthaburi 11000, Thailand, Tel.: +66 2 951 1485, Fax: +66 2 951 1486, E-mail: matsuo@dmsc.moph.go.th

BACKGROUND: Safe and live recombinant vector-based vaccine has advantages for HIV/AIDS vaccine development and a consecutive immunization regimen also seems desirable for inducing long-lasting immunities against HIV-1. Moreover, highly conserved Gag antigen of HIV is one of the most appropriate candidate to induce HIV-specific cytotoxic T lymphocyte (CTL) which may have implication in vaccine development. To develop Gag-targeted recombinant vaccine, we constructed two kinds of whole Gag antigen-expressing recombinant live vector vaccines using Mycobacterium bovis BCGTokyo (BCGTokyo ) and highly attenuated vaccinia virus DIs strain which is nonreplicative in human (Tagaya et al., Nature 1961), respectively.

METHODS: Gag gene of HIV-1 subtype B was amplified by PCR using pNL432 plasmid as a template. The gene was subcloned to hsp6O promoter-based mycobacteria-Escherichia coli shuttle plasmid and introduced into BCG. On the other hand, the gag gene transfer vector for vaccinia virus DIs strain was constructed by inserting the gene downstream of p7.5 promoter and introduced into virus genome by homologous recombination. Gag gene expression was confirmed by Western blot assay for lysates of recombinant BCG (rBCG) and recombinant vaccinia virus (rVV)-infected chicken embryonic fibroblast cells, respectively. Gag-specific immune response was analyzed in guinea pigs and mice to evaluate potential immunogenicity of these candidate vaccines.

RESULTS: We have successfully obtained both rBCG-HIV and rVVDIs -HIV clones that significantly express HIV Gag antigen. Guinea pigs which were immunized with Gag-expressing rBCG induced lymphocyte proliferation (LP) and delayed-type hypersensitivity (Th1 type) reactions against recombinant Gag antigen. The Gag-expressing rVVDIs could induce remarkable LP and CTL reactions specific to Gag antigen in Balb/c mice. We discuss the effect of the consecutive immunization of the vaccines.

CONCLUSION: Recombinant live vectors may be applicable to T cell-oriented HIV/AIDS vaccine, because both vectors were proved to be safe for human. Prime and boost regimen is also examined to study if it results in inducing higher efficiency of HIV-specific immune induction by combination of these recombinant vector-based vaccines that are cheap and easily available. We discuss advantages of the consecutive immunization regimen of the vaccines.

Keywords: AEGIS, HIV-1, Vaccinia virus, AIDS Vaccines, Mycobacterium bovis, Gene Products, gag, HIV Infections, Genes, gag, Vaccines, Synthetic, T-Lymphocytes, Cytotoxic, Immunization, Vaccines, Attenuated, Animal, Human, Mice, genetics, immunologyKWDaegis,hiv-1,vacciniavirus,aidsvaccines,mycobacteriumbovis,geneproducts,gag,hivinfections,genes,gag,vaccines,synthetic,t-lymphocytes,cytotoxic,immunization,vaccines,attenuated,animal,human,mice,genetics,immunology
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TuOrA293

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