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Background Immunodominance and sequence diversity are major hurdles in the development of effective HIV vaccines. We tested the hypothesis that a vaccine candidate composed of strictly Conserved Elements (CE) of the HIV proteome excluding the variable regions would help overcome problems of viral sequence diversity and potential negative effects of immunodominance. Seven CE were identified in p24. Vaccination of macaques with p55DNA failed to elicit cellular or humoral immune responses to the CE, while epitopes outside of the CE were immunogenic.

Results The mean pairwise AA diversity among the 66 SIVMAC251 Env sequences was 0.38%, and they differed from the vaccine strain SIV SME543 (Env) by 21.94%. The repeated low-dose challenge resulted in infections with an average of 1.7 founder variants with no evidence that the vaccine restricted the number of variants (p = 0.813). We explored whether the vaccine induced a sieve effect, i.e. whether breakthrough viruses differed between the vaccine and control groups. There was no difference for full-length Env sequences. Focusing on Env segments preferentially recognized by vaccinated monkeys in antibody arrays, we identified a sieve effect in the Env-V2 segment AA163-193: sequences from vaccinated animals were more divergent from the vaccine SIVSME543 or from the challenge stock SIVMAC251 than sequences in control animals (p ≤ 0.002).

Open Access Oral presentation OA06-06 LB. Evidence of vaccine-induced changes in breakthrough HIV-1 strains from the Step trial M Rolland1, S Tovanabutra2, PB Gilbert3, E Sanders-Buell2, L Heath1, AC deCamp3, CC Magaret3, M Bose2, A Bradfield2, A O'Sullivan2, J Crossler2, W Deng1, H Zhao1, K Wong1, DN Raugi1, J Hural3, S Dubey3, N Frahm3, NL Michael4, J Shiver5, L Corey3, F Li3, SG Self3, J Kim4, S Buchbinder6, DR Casimiro5, MN Robertson5, MJ McElrath3, FE McCutchan4 and JI Mullins*1

Address: 1Hospital Germans Trias i Pujol, IrsiCaixa AIDS Research Institute-HIVACAT, Badalona, Spain, 2'Lluita contra la Sida' Foundation, Hospital Germans Trias i Pujol, Badalona, Spain, 3Department of Microbiology. University of Washington, Washigton, USA, 4Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 5Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA, USA and 6Microsoft Research, Redmond, CA, USA * Corresponding author