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Retrovirology

Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

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

  • S Sina2,
  • S Tovanabutra2,
  • E Sanders-Buell2,
  • A Bates2,
  • M Bose2,
  • S Howell2,
  • G Ibitamuno2,
  • M Lazzaro2,
  • A O'Sullivan2,
  • J Lee2,
  • T Cervenka2,
  • J Kuroiwa2,
  • K Baldwin2,
  • DH Barouch1,
  • M Robb2,
  • R O'Connell2,
  • NL Michael2,
  • JH Kim2 and
  • M Rolland2
Retrovirology20129(Suppl 2):O32

https://doi.org/10.1186/1742-4690-9-S2-O32

Published: 13 September 2012

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.

Authors’ Affiliations

(1)
BIDMC, Harvard Medical School, and Ragon Institute, Boston, USA
(2)
U.S. Military HIV Research Program/Henry M. Jackson Foundation, Bethesda, USA

Copyright

© Sina et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://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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