Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

rAd5/NYVAC-B is superior to NYVAC-B/rAd5 and is dependent on rAd5 dose for neutralizing antibody responses against HIV-1

  • DC Montefiori1,
  • Y Huang2,
  • S Karuna3,
  • M Allen4,
  • N Kochar2,
  • S Chappuis5,
  • J Gaillard5,
  • G Tomaras1,
  • B Graham6,
  • P Bart5 and
  • G Pantaleo5
Retrovirology20129(Suppl 2):P132

https://doi.org/10.1186/1742-4690-9-S2-P132

Published: 13 September 2012

Background

HVTN 078 is a phase 1b clinical trial of heterologous vector prime/boost vaccine regimens (NYVAC-B/rAd5 vs. rAd5/NYVAC-B) in healthy, HIV-1 uninfected, Ad5 seronegative adults. The rAd5 expressed a clade B Gag-Pol fusion protein and secreted gp140s of HIV-1 strains 92RW020 (clade A), HxB2/Bal-V3/ V1V2 (clade B) and 97ZA012 (clade C). The NYVAC-B expressed a clade B Gag-Pol-Nef polyprotein and the secreted gp120 of Bx08 (clade B). A total of 80 participants were randomized into a placebo group (P) and four treatment groups: T1, 2x NYVAC-B/1x rAd5 (1010); T2, 1x rAd5 (108)/2x NYVAC-B; T3, 1x rAd5 (109)/2x NYVAC-B; T4, 1x rAd5 (1010)/2x NYVAC-B.

Methods

Binding and neutralizing antibodies were assessed at 2 weeks post-final boosting. Neutralization was assessed with tier 1 and tier 2 Env-pseudotyped viruses in TZM-bl cells, and with tier 2 Env.IMC.LucR viruses in A3R5 cells.

Results

A dose effect for increasing anti-Env binding antibodies was seen, with higher doses of rAd5 being optimal. For neutralizing antibodies, positive response rates/median titers across the treatment groups were highest against MN.3 (69.3%/116) followed by SF162.LS (42.1%/54), BaL.26 (18.4%/15.5), MW965.26 (14.5%/31) and Bx08.16 (11.8%/19.5). Five subjects neutralized all 5 tier 1 viruses, 5 subjects neutralized 4 viruses, 7 subjects neutralized 3 viruses, 14 subjects neutralized 2 viruses (MN.3 and SF162.LS) and 18 subjects neutralized 1 virus (MN.3). Aggregate magnitude-breadth scores across the tier 1 panel were strongest for T4 followed by T3, T1 and T2. Differences were significant for T1 vs. T3 (p=0.048) and T1 vs. T4 (p=0.004). Responses against tier 2 viruses were weak and sporadic in the A3R5 assay and were nearly absent in the TZM-bl assay.

Conclusion

A 1010 dose of rAd5 was superior to the two lower doses of 109 and 108 for both binding and neutralizing antibodies. At the highest rAd5 dose tested, rAd5/NYVAC-B was superior to NYVAC-B/rAd5 for neutralizing antibodies.

Authors’ Affiliations

(1)
Duke University Medical Center
(2)
SCHARP
(3)
Fred Hutchinson Cancer Research Center/HVTN
(4)
NIAID-NIH
(5)
Lausanne University Hospital
(6)
Vaccine Research Center, NIH

Copyright

© Montefiori 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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