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Title: Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection
Authors: Sarah Auclair
Fengliang Liu
Qingli Niu
Wei Hou
Gavin Churchyard
Cecilia Morgan
Nicole Frahm
Sorachai Nitayaphan
Punnee Pitisuthithum
Supachai Rerks-Ngarm
Jason T. Kimata
Lynn Soong
Genoveffa Franchini
Merlin Robb
Jerome Kim
Nelson Michael
Haitao Hu
International Vaccine Institute, Seoul
Wuhan University
Thailand Ministry of Public Health
UT Medical Branch at Galveston
National Cancer Institute
Walter Reed Army Institute of Research
Mahidol University
Royal Thai Army
Fred Hutchinson Cancer Research Center
Baylor College of Medicine
Aurum Institute
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 1-Feb-2018
Citation: PLoS Pathogens. Vol.14, No.2 (2018)
Abstract: © 2018 Library of Science. All Rights Reserved. The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination.
ISSN: 15537374
Appears in Collections:Scopus 2018

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