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Title: Modulation of vaccine-induced CD4 T cell functional profiles by changes in components of HIV vaccine regimens in humans
Authors: Franco Pissani
Bianca Schulte
Michael A. Eller
Bruce T. Schultz
Silvia Ratto-Kim
Mary Marovich
Prasert Thongcharoen
Somchai Sriplienchan
Supachai Rerks-Ngarm
Punnee Pitisuttithum
Stefan Esser
Galit Alter
Merlin L. Robb
Jerome H. Kim
Nelson L. Michael
Hendrik Streeck
International Vaccine Institute, Seoul
Massachusetts General Hospital
National Institute of Allergy and Infectious Diseases
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Walter Reed Army Institute of Research
Mahidol University
Faculty of Medicine, Siriraj Hospital, Mahidol University
Universitäts Klinikum Essen und Medizinische Fakultät
Mabtech, Inc.
Keywords: Agricultural and Biological Sciences;Immunology and Microbiology
Issue Date: 1-Jan-2018
Citation: Journal of Virology. Vol.92, No.23 (2018)
Abstract: Copyright © 2018 American Society for Microbiology. All Rights Reserved. To date, six vaccine strategies have been evaluated in clinical trials for their efficacy at inducing protective immune responses against HIV infection. However, only the ALVAC-HIV/AIDSVAX B/E vaccine (RV144 trial) has demonstrated protection, albeit modestly (31%; P 0.03). One potential correlate of protection was a low-frequency HIV-specific CD4 T cell population with diverse functionality. Although CD4 T cells, particularly T follicular helper (Tfh) cells, are critical for effective antibody responses, most studies involving HIV vaccines have focused on humoral immunity or CD8 T cell effector responses, and little is known about the functionality and frequency of vaccine-induced CD4 T cells. We therefore assessed responses from several phase I/II clinical trials and compared them to responses to natural HIV-1 infection. We found that all vaccines induced a lower magnitude of HIV-specific CD4 T cell responses than that observed for chronic infection. Responses differed in functionality, with a CD40 ligand (CD40L)-dominated response and more Tfh cells after vaccination, whereas chronic HIV infection provoked tumor necrosis factor alpha (TNF-)-dominated responses. The vaccine delivery route further impacted CD4 T cells, showing a stronger Th1 polarization after dendritic cell delivery than after intramuscular vaccination. In prime/boost regimens, the choice of prime and boost influenced the functional profile of CD4 T cells to induce more or less polyfunctionality. In summary, vaccine-induced CD4 T cell responses differ remarkably between vaccination strategies, modes of delivery, and boosts and do not resemble those induced by chronic HIV infection. Understanding the functional profiles of CD4 T cells that best facilitate protective antibody responses will be critical if CD4 T cell responses are to be considered a clinical trial go/no-go criterion.
ISSN: 10985514
Appears in Collections:Scopus 2018

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