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

Significance Efforts to develop an efficacious HIV vaccine have been unsuccessful to date. Efficacy trials have reported that recombinant Ad5 (rAd5)-HIV vaccines were not efficacious and unexpectedly associated with excess HIV infection in vaccine recipients. Understanding the underlying mechanisms...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-09, Vol.111 (37), p.13439-13444
Main Authors: Hu, Haitao, Eller, Michael A., Zafar, Shah, Zhou, Yu, Gu, Mengnan, Wei, Zhi, Currier, Jeffrey R., Marovich, Mary A., Kibuuka, Hannah N., Bailer, Robert T., Koup, Richard A., Robb, Merlin L., Michael, Nelson L., Kim, Jerome H., Ratto-Kim, Silvia
Format: Article
Language:English
Subjects:
Adenoviridae - immunology
Adenovirus
Adenoviruses
AIDS vaccines
AIDS Vaccines - immunology
Antigens
Biological Sciences
CD4-Positive T-Lymphocytes - immunology
Clinical trials
Cytokines
Cytomegalovirus - immunology
Disease Susceptibility
Genotype & phenotype
Healthy Volunteers
HIV
HIV infections
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
Human cytomegalovirus
Human immunodeficiency virus
Humans
Infections
Inflammation - pathology
Interleukin-17 - biosynthesis
Interleukin-2 - biosynthesis
Intestinal Mucosa - pathology
Phenotype
Phenotypes
Recombination, Genetic - genetics
Species Specificity
T cell receptors
T lymphocytes
Th17 Cells - immunology
Vaccination
Vaccines
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Summary:Significance Efforts to develop an efficacious HIV vaccine have been unsuccessful to date. Efficacy trials have reported that recombinant Ad5 (rAd5)-HIV vaccines were not efficacious and unexpectedly associated with excess HIV infection in vaccine recipients. Understanding the underlying mechanisms is urgent and will further HIV vaccine design. By comparing human CD4 T cells specific to Ad5 and CMV, we report that natural exposure- or vaccine-induced Ad5-specific CD4 T cells are highly susceptible to HIV compared with CMV-specific CD4 T cells and selectively manifest a Th17-like proinflammatory phenotype. Our findings suggest a potential mechanism for rAd5-associated excess HIV infections in vaccine recipients and highlight that testing HIV susceptibility of vaccine-generated CD4 T cells may have utility before vaccine evaluation in human trials.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1400446111