A therapeutic HIV vaccine using coxsackie-HIV recombinants: a possible new strategy.
The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. A strategy to accomplish this goal is to use chemotherapy to reduce viral load followed by immunotherapy to stimulate HIV-specific immune responses that are observed in long-term asymptomatic individuals. An effective, live, recombinant virus, expressing HIV sequences, would be capable of inducing both CTL and CD4(+) helper T cell responses. To accomplish these goals, the viral vector must be immunogenic yet retain its avirulent phenotype in a T cell-deficient host. We have identified a coxsackievirus variant, CB4-P, that can induce protective immunity against a virulent variant. In addition, the CB4-P variant remains avirulent in mice lacking CD4(+) helper T cells, suggesting that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine. Two strategies designed to elicit CTL and CD4(+) helper T cell responses were used to construct CB4-P/HIV recombinants. Recombinant viruses were viable, genetically stable, and retained the avirulent phenotype of the parental virus. In designing a viral vector for vaccine development, an issue that must be addressed is whether preexisting immunity to the vector would affect subsequent administration of the recombinant virus. Using a test recombinant, we showed that prior exposure to the parental CB4-P virus did not affect the ability of the recombinant to induce a CD4(+) T cell response against the foreign sequence. The results suggest that a "cocktail" of coxsackie/HIV recombinants may be useful as a therapeutic HIV vaccine.
Halim
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SS
Department of Biomedical Sciences, School of Public Health, State University of New York at Albany, Albany, New York 12237, USA.
Collins
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DN
Ramsingh
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AI
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral; D004770:Enterovirus / Q000276:immunology* / Q000472:pathogenicity; D015870:Gene Expression; D014644:Genetic Variation; D005822:Genetic Vectors / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000628:therapy*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020815:Polyproteins / Q000276:immunology; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic / Q000627:therapeutic use; D014774:Virulence
D016915:AIDS Vaccines; D004279:DNA, Viral; D016655:HIV Core Protein p24; D020815:Polyproteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic