Immune Competition of HIV Epitopes in Draining Lymph Nodes

Abstract

Abstract Background Using HIV-derived DNAs encoding only conserved elements (CE) within Gag or Env, we were able to alter the immune hierarchy redirecting to otherwise subdominant viral targets. This hierarchy was preserved after boosting with DNA expressing full-length (FL) Gag or Env proteins. A vaccination strategy including simultaneous delivery of CE and FL molecules in separate anatomical sites was compared to CE prime/co-delivery CE+FL booster vaccination to examine the magnitude and breadth of epitope recognition to variable and conserved regions. Methods The DNA vaccine components were administered by IM route followed by in vivo electroporation in macaques. Antigen-specific cellular immune responses in blood were monitored by flow cytometry. Results The T cell responses targeting CE were similar in magnitude, function and breadth in both regimens. Separating anatomical sites of vaccination CE resulted in increased levels of cytotoxic T cell responses targeting variable regions. Thus, separating the immunogens allows development of T cell responses with overall increased breadth including conserved and variable epitopes. Conclusion The CE prime/CE+FL DNA boost vaccine induces immune responses targeting the CE epitopes. The vaccination strategy that separates CE and FL DNA plasmids to different anatomical sites, thereby targeting different draining lymph nodes, induces responses to both CE and variable regions. This vaccine regimen has the advantage of avoiding interference of the different vaccine components (CE, FL) during the priming of the adaptive immune response, redirecting immune dominance, and eliciting robust cytotoxic T cell responses targeting conserved and variable regions in the viral proteome.