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Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans

Abstract

The immunologic basis for the potential enhanced HIV-1 acquisition in adenovirus serotype 5 (Ad5)-seropositive individuals who received the Merck recombinant Ad5 HIV-1 vaccine in the STEP study remains unclear. Here we show that baseline Ad5-specific neutralizing antibodies are not correlated with Ad5-specific T lymphocyte responses and that Ad5-seropositive subjects do not develop higher vector-specific cellular immune responses as compared with Ad5-seronegative subjects after vaccination. These findings challenge the hypothesis that activated Ad5-specific T lymphocytes were the cause of the potential enhanced HIV-1 susceptibility in the STEP study.

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Figure 1: Adenovirus-specific humoral and cellular immune responses before and after rAd5-Gag vaccination.
Figure 2: Magnitude and phenotype of adenovirus-specific and total CD4+ T lymphocyte subpopulations before and after 1 × 1011 vp rAd5-Gag vaccination.

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Acknowledgements

We thank J. Custers, M. Pau, P. Abbink, A. La Porte, N. Letvin, F. Stephens and T. Swanson for generous advice and assistance. We acknowledge support from the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (38614) and the US National Institutes of Health (AI066305, AI066924, AI078526, AI074078 and AI076066).

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Contributions

K.L.O. and J.L. performed and analyzed the cellular immunologic assays. S.L.K. and Y.-H.S. performed and analyzed the humoral immunologic assays. J.E.S., M.A.L., N.A.H. and M.R.B. provided reagents and performed flow cytometric assays. S.A.D., J.W.S., M.N.R. and D.R.C. provided clinical samples and participated in the design of the study. J.G. provided vectors and participated in the design of the study. D.H.B. led the design and conduct of the study. All coauthors discussed the data and contributed to writing the manuscript.

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Correspondence to Dan H Barouch.

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Supplementary Figs. 1–4 and Supplementary Methods (PDF 486 kb)

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O'Brien, K., Liu, J., King, S. et al. Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans. Nat Med 15, 873–875 (2009). https://doi.org/10.1038/nm.1991

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