Brarouch, D. H.,O'Brien, K. L.,Simmons, N. L.,King, S. L.,Abbink, P.,Maxfield, L. F.,Sun, Y. H.,La Porte, A.,Riggs, A. M.,Lynch, D. M.,Clark, S. L.,Backus, K.,Perry, J. R.,Deaman, M. S.,Carville, A.,Mansfield, K. G.,Szinger, J. J.,Fischer, W.,Muldoon, M.,Korber, B.

The worldwide diversity of HIV-1 presents an unprecedented challenge for vaccine development(1,2). Antigens derived from natural HIV-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. Polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global HIV-1 sequence diversity(3). Here we show that mosaic HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors markedly augmented both the breadth and depth without compromising the magnitude of antigen-specific T lymphocyte responses as compared with consensus or natural sequence HIV-1 antigens in rhesus monkeys. Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1.