confer enhanced immune coverage of diverse HIV strains in monkeys.

Mosaic vaccines elicit CD8(+) T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys.

An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses. 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 virus. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents a key challenge for creating an HIV vaccine. 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 isolates. Here Santra and colleagues immunized rhesus monkeys by plasmid DNA prime and recombinant vaccinia virus boost with vaccine constructs expressing either consensus or polyvalent mosaic proteins. As compared to consensus immunogens, the mosaic immunogens elicited CD8(+) T lymphocyte responses to more epitopes of each viral protein than did 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

In this macaque study, a mosaic immunogen was created by combining the gag and nef genes from geographically and sub-type diverse natural strains of HIV. A much broader immune response was elicited in macaques with this recombinant mix than with a consensus protein. Cellular immune responses to mosaic immunogens recognized a greater diversity of viral epitope variants, with CD+8 T lymphocytes showing significantly greater cross-reactivity, not only to more epitopes but also to more variant sequences of specific epitopes. Keeping up with viral evolution means expanding the breadth and depth of our CD8+ cytotoxic T lymphocyte responses – it looks like mosaic vaccines may be able to give us the leg up that we