View All Abstracts for Session 40
219 Coxsackievirus as a Vector for a Therapeutic HIV Vaccine
A.I. Ramsingh*
Wadsworth Ctr., New York State Dept. of Hlth., Albany, USA
Background: The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. This might be accomplished by using antiretroviral therapy to reduce viral load followed by vaccination to elicit HIV-specific immune responses observed in long-term asymptomatic individuals. Since these responses include gag-specific CTL and CD4+ T-helper-cell responses, a possible vaccine strategy is the expression of p24 sequences within a live-attenuated viral vector.
Methods: Two strategies, designed to elicit CTL and CD4+ T-helper-cell responses, were used to express foreign sequences (ovalbumin, gag p24) within coxsackievirus B4, CB4-P. The recombinants were assessed for genetic stability, replication competence, and physical stability. The immunogenicity of a test recombinant was assessed.
Results: The attenuated yet immunogenic nature of CB4-P suggests that it might be useful as a vaccine vector. To explore this possibility, gag p24 and ovalbumin sequences were expressed in CB4-P. CB4-P recombinants expressing short peptides within a capsid protein or longer sequences at the amino terminus of the viral polyprotein were thermostable, genetically stable, and replication competent. Splenic CD4+ T cells from mice infected with CB4-P/ova10 proliferated in response to an ovalbumin peptide indicating that the recombinant could elicit a T-cell response against the foreign sequence. A concern of using recombinant viruses as vaccines is whether pre-existing immunity to wild-type virus prevents the recombinant from inducing immunity. To address this, mice were infected with CB4-P and then with CB4-P/ova10. Splenic CD4+ T cells from the doubly infected mice proliferated in response to an ovalbumin peptide suggesting that pre-existing immunity to the wild-type virus did not prevent the recombinant from eliciting an immune response against the foreign sequence.
Conclusions: The CB4-P variant retains its avirulent phenotype in wild-type mice and in mice lacking CD4+ T-helper cells. The CB4-P variant can induce protective immunity against a virulent variant. The CB4-P variant can be used as a vector to express foreign sequences so that T-cell responses are elicited against the inserted sequences. The results suggest that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine.
Contact Author about this Abstract
