A Therapeutic HIV Vaccine Using Coxsackie–HIV Recombinants: A Possible New Strategy
| Autor: | Arlene I. Ramsingh, Sadia S. Halim, Doris N. Collins |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cellular immunity
Genetic Vectors Molecular Sequence Data Immunology HIV Core Protein p24 Gene Expression HIV Infections Mice Transgenic Vaccines Attenuated Recombinant virus Virus Viral vector Mice Virology Animals Humans HIV vaccine Enterovirus Polyproteins AIDS Vaccines Mice Knockout Mice Inbred BALB C Vaccines Synthetic Base Sequence Virulence biology Genetic Variation biology.organism_classification Infectious Diseases Helper virus DNA Viral Lentivirus Viral load HeLa Cells |
| Zdroj: | AIDS Research and Human Retroviruses. 16:1551-1558 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/088922200750006074 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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