Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

rAd5 prime/NYVAC-B boost regimen is superior to NYVAC-B prime/rAd5 boost regimen for both response rates and magnitude of CD4 and CD8 T-cell responses

  • P Bart1,
  • Y Huang2,
  • N Frahm3,
  • S Karuna3,
  • M Allen4,
  • NK Kochar3,
  • S Chappuis1,
  • J Gaillard1,
  • B Graham5 and
  • G Pantaleo1
Retrovirology20129(Suppl 2):O72

DOI: 10.1186/1742-4690-9-S2-O72

Published: 13 September 2012

Background

HVTN 078 is a randomized, double blind phase 1b clinical trial to evaluate the safety and immunogenicity of heterologous prime/boost vaccine regimens (NYVAC-B/rAd5 vs. rAd5/NYVAC-B) in healthy, HIV-1 uninfected, Ad5 seronegative adult participants.

Methods

The rAd5 vaccine expressed clade B Gag-Pol and the gp140 of HIV-1 92RW020 (clade A), HxB2/Bal-V3/ΔV1V2 (clade B) and 97ZA012 (clade C). The NYVAC-B vaccine expressed clade B Gag-Pol-Nef and the gp120 of Bx08 (clade B). 80 healthy, HIV-1 uninfected, Ad5 seronegative volunteers, aged 18 to 45 years, were randomized to the placebo arm (n=5) or one of 4 treatment (T) arms: T1 (n=30), 2xNYVAC-B/1xrAd5 (10E10); T2 (n=15), 1xrAd5 (10E8)/2xNYVAC-B; T3 (n=15), 1xrAd5 (10E9)/2xNYVAC-B; T4 (n=15), 1xrAd5 (10E10)/2xNYVAC-B.

Intracellular cytokine staining responses (percent of CD4+ and CD8+ T cells producing IFN-γ and/or IL-2 in response to stimulation with global PTE peptides) were assessed two weeks after the final vaccination.

Results

For CD4+ T cells, the overall response rates for IFN-γ and/or IL-2 among the vaccinees were 42.9%, 93.3%, 92.3%, and 85.7% for T1-T4, respectively; and the median response magnitudes for positive responders were 0.26%, 0.76%, 0.40%, and 0.76% for T1- T4, respectively. Both response rates (p<0.01) and magnitudes (p<0.03) of CD4+ T-cell responses were significantly lower in T1 compared to the other three treatment groups. For CD8+ T cells, the overall response rates were 65.5%, 73.3%, 76.9% and 85.7% for T1-T4, respectively; and median response magnitudes for positive responders were 0.32%, 0.99%, 1.86%, and 1.65%, respectively. Response rates were not significantly different between groups; however, response magnitudes were significantly lower in T1 compared to the other three arms (p<0.04).

Conclusion

Priming with rAd5 followed by NYVAC-B boost is superior to priming with NYVAC-B followed by rAd5 boost for both response rates and the magnitude of CD4+ and CD8+ T-cell responses.

Authors’ Affiliations

(1)
CHUV
(2)
SCHARP
(3)
HVTN
(4)
DAIDS, NIAID, NIH
(5)
Vaccine Research Center, NIAID, NIH

Copyright

© Bart 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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