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Title: RV144 HIV-1 vaccination impacts postinfection antibody responses
Authors: Thembi Mdluli
Ningbo Jian
Bonnie Slike
Dominic Paquin-Proulx
Gina Donofrio
Aljawharah Alrubayyi
Syna Gift
Rebecca Grande
Mary Bryson
Anna Lee
Vincent Dussupt
Letzibeth Mendez-Riveria
Eric Sanders-Buell
Agnès Laurence Chenine
Ursula Tran
Yifan Li
Eric Brown
Paul T. Edlefsen
Robert O'Connell
Peter Gilbert
Sorachai Nitayaphan
Punnee Pitisuttihum
Supachai Rerks-Ngarm
Merlin L. Robb
Robert Gramzinski
Galit Alter
Sodsai Tovanabutra
Ivelin S. Georgiev
Margaret E. Ackerman
Victoria R. Polonis
Sandhya Vasan
Nelson L. Michael
Jerome H. Kim
Michael A. Eller
Shelly J. Krebs
Morgane Rolland
Vanderbilt University Medical Center
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Walter Reed Army Institute of Research
Mahidol University
Dartmouth College
Ragon Institute
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 8-Dec-2020
Citation: PLoS Pathogens. Vol.16, No.12 (2020)
Abstract: © 2020 Mdluli et al. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Abdependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.
ISSN: 15537374
Appears in Collections:Scopus 2020

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