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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).

Evidence for Env-V2 sieve effect in breakthrough SIV MAC251 infections in rhesus monkeys vaccinated with Ad26/MVA and MVA/Ad26 constructs