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Volume 9 Supplement 2

AIDS Vaccine 2012

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

Background

We had previously shown that rhesus monkeys receiving Ad26/MVA and MVA/Ad26 vaccines expressing SIVSME543 were protected against SIVMAC251 challenge (doi:10.1038/nature10766). Protection was associated with Env-specific binding ELISA antibody responses, including V2-specific antibodies.

Methods

We amplified 66 sequences from the SIV MAC251 challenge stock, and 409 near-full length genomes from 13 vaccine and 13 control monkeys. A series of pre-specified phylogenetic and statistical tests for sieve effects was performed.

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).

Conclusion

The sieve effect in Env-V2, combined with Env-V2-specific binding antibodies identified as a correlate of protection against SIV MAC251 acquisition in the study, provide evidence supporting the importance of protective responses directed against the Env-V2 region.

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Correspondence to M Rolland.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sina, S., Tovanabutra, S., Sanders-Buell, E. et al. Evidence for Env-V2 sieve effect in breakthrough SIV MAC251 infections in rhesus monkeys vaccinated with Ad26/MVA and MVA/Ad26 constructs. Retrovirology 9, O32 (2012). https://doi.org/10.1186/1742-4690-9-S2-O32

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Keywords

  • Rhesus Monkey
  • Control Monkey
  • Antibody Array
  • Breakthrough Virus
  • Sieve Effect