Mosaic Vaccines Elicit CD8+ T lymphocyte Responses in Monkeys that Confer Enhanced Immune Coverage of Diverse HIV Strains

An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses1, 2. It must generate CD8+ T lymphocytes that control HIV replication and CD4+ T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus3–5. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents an important challenge for creating an AIDS vaccine6, 7. Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates8. In the present study we immunized rhesus monkeys by plasmid DNA prime/ recombinant vaccinia virus boost using vaccine constructs expressing either consensus or polyvalent mosaic proteins. The mosaic immunogens elicited CD8+ T lymphocyte responses to more epitopes of each viral protein than the consensus immunogens, and to more variant sequences of CD8+ T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.