A successful HIV vaccine will likely have to elicit protective T helper, T cytotoxic, and B cell responses. The current proposal focuses on T cell immunity to HIV using a live, recombinant enterovirus. We have identified an enterovirus, a coxsackievirus, that is highly attenuated yet immunogenic. The application addresses the development of coxsackievirus as a vaccine vector for HIV and is a proof-of-concept proposal. One goal of the study is the construction of coxsackie/HIV recombinants which will elicit HIV-specific T helper and T cytotoxic responses. Two strategies will be used to construct recombinants capable of inducing both types of T cell response. To elicit T helper cell responses, HIV peptides will be expressed within a capsid protein of coxsackievirus. To generate T cytotoxic cell responses, HIV sequences will be expressed in infected cells but will not be incorporated into progeny virions. Another goal of the study is to evaluate the immunogenicity of the coxsackie/HIV recombinants in mice. Can the recombinants induce HIV-specific T helper and T cytotoxic cell responses? The final goal of the study is to identify parameters that are able to augment the immune responses. Does the route of infection influence the magnitude of the T helper and T cytotoxic cell responses? Can T cell immunity be augmented with cytokine adjuvants? The results obtained from this work will provide the framework for developing appropriate recombinants for testing in a non-human primate model in a later study. Recombinants that can elicit T cell immunity against HIV could be part of a """"""""cocktail"""""""" of immunogens used as a preventive HIV vaccine.
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