Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals

Haitao Hu, Michael A. Eller, Shah Zafar, Yu Zhou, Mengnan Gu, Zhi Wei, Jeffrey R. Currier, Mary A. Marovich, Hannah N. Kibuuka, Robert T. Bailer, Richard A. Koup, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Silvia Ratto-Kim

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Efficacy trials of adenovirus 5-vectored candidate HIV vaccines [recombinant Ad5 (rAd5)-HIV] were halted for futility due to lack of vaccine efficacy and unexpected excess HIV infections in the vaccine recipients. The potential immunologic basis for these observations is unclear. We comparatively evaluated the HIV susceptibility and phenotypes of human CD4 T cells specific to Ad5 and CMV, two viruses that have been used as HIV vaccine vectors. We show that Ad5-specific CD4 T cells, either induced by natural Ad5 exposure or expanded by rAd5 vaccination, are highly susceptible to HIV in vitro and are preferentially lost in HIV-infected individuals compared with CMV-specific CD4 T cells. Further investigation demonstrated that Ad5-specific CD4 T cells selectively display a proinflammatory Th17-like phenotype and express macrophage inflammatory protein 3α and α4β7 integrin, suggestive of gut mucosa homing potential of these cells. Analysis of HIV p24 and cytokine coexpression using flow cytometry revealed preferential infection of IL-17- and IL-2-producing, Ad5-specific CD4 T cells by HIV in vitro. Our data suggest a potential mechanism explaining the excess HIV infections in vaccine recipients after rAd5-HIV vaccination and highlight the importance of testing the HIV susceptibility of vaccine-generated, vector and insert-specific CD4 T cells in future HIV vaccine studies.

Original languageEnglish (US)
Pages (from-to)13439-13444
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number37
DOIs
StatePublished - Sep 16 2014
Externally publishedYes

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Keywords

  • AIDS
  • Antigen-specific CD4 T cells
  • Viral vectors

ASJC Scopus subject areas

  • General

Cite this

Hu, H., Eller, M. A., Zafar, S., Zhou, Y., Gu, M., Wei, Z., Currier, J. R., Marovich, M. A., Kibuuka, H. N., Bailer, R. T., Koup, R. A., Robb, M. L., Michael, N. L., Kim, J. H., & Ratto-Kim, S. (2014). Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals. Proceedings of the National Academy of Sciences of the United States of America, 111(37), 13439-13444. https://doi.org/10.1073/pnas.1400446111