DNA Vaccine–Induced Long-Lasting Cytotoxic T Cells Targeting Conserved Elements of Human Immunodeficiency Virus Gag Are Boosted Upon DNA or Recombinant Modified Vaccinia Ankara Vaccination

Abstract

We developed DNA-based vaccines able to induce efficient cytotoxic T cell responses targeting conserved elements (CE) of HIV-1 Gag. These CE were selected by stringent conservation, the ability to induce T cell responses with broad HLA coverage and the association between recognition of CE epitopes and viral control in HIV-infected individuals. Based on homology to HIV, we also developed an SIV p27gag CE DNA vaccine. In this study, we report on the durability of the CE-specific T cell responses induced by HIV and SIV CE DNA-based prime/boost vaccine regimens in rhesus macaques and show that the initially primed CE-specific T cell responses were efficiently boosted by a single CE DNA vaccination after the long rest period (up to two years). In another cohort of animals, we show that a single inoculation with a non-replicating recombinant Modified Vaccinia Ankara (rMVA62B) also potently boosted CE-specific responses after ~1.5 years of rest. Both, CE DNA or rMVA62B booster vaccinations increased the magnitude and cytotoxicity of the CE-specific responses while maintaining the breadth of CE recognition. Env produced by rMVA62B did not negatively interfere with the recall of the Gag CE responses. rMVA62B could be beneficial to further boosting the immune response to Gag in humans. Vaccine regimens that employ CE DNA as a priming immunogen hold promise for application in HIV prevention and therapy.