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Volume 6 Supplement 3

AIDS Vaccine 2009

P17-22. Impact of rare adenovirus seroprevalence on HIV-1 acquisition in the Step study

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Background

In the phase IIb Step study, vaccinees with baseline Ad5-specific neutralizing antibodies (NAbs) exhibited a potential increased rate of HIV-1 acquisition as compared with placebo controls. We sought to evaluate whether baseline Ad5 NAbs correlated with NAbs to non-type C rare Ad serotypes and whether baseline NAbs to rare Ad serotypes correlated with enhancement of HIV-1 acquisition after rAd5-gag/pol/nef vaccination.

Methods

In a case-controlled study, baseline sera from 81 cases who acquired HIV-1 infection during the Step study (52 vaccinees and 29 placebo recipients) and 324 non-cases who did not acquire HIV-1 infection (208 vaccinees and 29 placebo recipients) were evaluated for Ad5, Ad26, Ad35, and Ad48 NAb titers. Non-cases were randomly selected and matched for treatment arm, Ad5 serostatus, circumcision status, and geographic region.

Results

Baseline Ad5 seroprevalence was 58% in these samples with a median titer of 702. In contrast, baseline Ad26, Ad35, and Ad48 seroprevalence was 14%, 6%, and 17%, respectively, with median titers of 49, 47, and 46. There were no correlations between baseline Ad5 NAbs and Ad26/35/48 NAbs (P = 0.44–0.77, Spearman rank correlation tests). Moreover, there were no differences observed in baseline Ad26/35/48 NAbs between cases and non-cases (P = 0.46–0.97, Wilcoxon rank sum tests).

Conclusion

Ad5 NAbs and Ad26/35/48 NAbs were independent variables that did not co-segregate, indicating that Ad5 NAbs were not a surrogate marker for and did not predict NAbs to these rare Ad serotypes. In addition, no increased HIV-1 acquisition was observed in subjects with baseline Ad26/35/48 NAbs following rAd5 vaccination. These data suggest that cross-reactive immunity against heterologous Ad serotypes did not contribute to increased HIV-1 susceptibility in this study. These findings have important implications for the development of rare serotype Ad vector-based vaccines for HIV-1.

Acknowledgements

NIAID/HVTN, NIAID/IPCAVD, Gates/CAVD.

Author information

Correspondence to LF Maxfield.

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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 2.0 International 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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Maxfield, L., King, S., Riggs, A. et al. P17-22. Impact of rare adenovirus seroprevalence on HIV-1 acquisition in the Step study. Retrovirology 6, P304 (2009) doi:10.1186/1742-4690-6-S3-P304

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Keywords

  • Placebo Recipient
  • Spearman Rank Correlation
  • Neutralize Antibody
  • Placebo Control
  • Spearman Rank Correlation Test