Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

Full-length HIV-1 immunogens induce greater T lymphocyte responses to conserved epitopes than conserved-region-only HIV-1 immunogens in monkeys

  • KE Stephenson1,
  • A SanMiguel1,
  • NL Simmons1,
  • K Smith1,
  • JJ Szinger2,
  • BT Korber2 and
  • DH Barouch1
Retrovirology20129(Suppl 2):O70

DOI: 10.1186/1742-4690-9-S2-O70

Published: 13 September 2012

Background

A global HIV-1 vaccine will need to induce broadly reactive immune responses against conserved HIV-1 regions. It is currently unclear how best to elicit these responses by vaccination. We therefore compared the immunogenicity of a bivalent full-length HIV-1 Gag/Pol/Env mosaic vaccine, a trivalent full-length HIV-1 Gag/Pol/Env mosaic vaccine, and a bivalent mosaic vaccine containing only conserved HIV-1 Gag/Pol/Env epitopes in rhesus monkeys.

Methods

We immunized 18 rhesus monkeys with rAd35 (prime) and rAd26 (boost) vectors expressing bivalent full-length (N=6), trivalent full-length (N=6), or bivalent conserved-region-only (N=6) HIV-1 Gag/Pol/Env mosaic immunogens. We assessed HIV-1-specific and conserved-region-specific cellular immune responses by ELISPOT using global PTE and vaccine-matched peptides. Responses were mapped to individual epitopes and were identified as CD4+ or CD8+ through cell-depletion assays. Comparisons were performed by Wilcoxon rank-sum tests.

Results

There was no difference in the breadth of HIV-1-specific T lymphocyte responses elicited by the bivalent and trivalent full-length mosaic vaccines (P=.686). However, the bivalent full-length vaccine generated a greater breadth of HIV-1-specific CD8+ T lymphocyte responses than the conserved-region-only vaccine (P=.007). The bivalent full-length vaccine also generated equivalent breadth of CD8+ T lymphocyte responses to conserved HIV-1 epitopes compared to the conserved-region-only vaccine (P=1.000), and surprisingly, the responses generated by the full-length vaccine to conserved HIV-1 epitopes were greater in magnitude than those generated by the conserved-region-only vaccine (P=.008).

Conclusion

These data demonstrate that an HIV-1 mosaic vaccine expressing full-length antigens elicited greater responses to conserved epitopes than a mosaic vaccine expressing only concatenated conserved HIV-1 regions. In addition, the bivalent and trivalent full-length mosaic vaccines generated comparable breadth of HIV-1-specific CD8+ T lymphocyte responses. These results support the clinical development of the bivalent full-length HIV-1 mosaic vaccine.

Authors’ Affiliations

(1)
Beth Israel Deaconess Medical Center and Harvard University
(2)
Los Alamos National Laboratory

Copyright

© Stephenson 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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