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Title: Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines
Authors: Amy W. Chung
Musie Ghebremichael
Hannah Robinson
Eric Brown
Ickwon Choi
Sophie Lane
Anne Sophie Dugast
Matthew K. Schoen
Morgane Rolland
Todd J. Suscovich
Alison E. Mahan
Larry Liao
Hendrik Streeck
Charla Andrews
Supachai Rerks-Ngarm
Sorachai Nitayaphan
Mark S. De Souza
Jaranit Kaewkungwal
Punnee Pitisuttithum
Donald Francis
Nelson L. Michael
Jerome H. Kim
Chris Bailey-Kellogg
Margaret E. Ackerman
Galit Alter
Massachusetts Institute of Technology
Thayer School of Engineering at Dartmouth
Dartmouth College
Walter Reed Army Institute of Research
Duke University
Thailand Ministry of Public Health
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Global Solutions for Infectious Diseases
Keywords: Medicine
Issue Date: 19-Mar-2014
Citation: Science Translational Medicine. Vol.6, No.228 (2014)
Abstract: The human phase 2B RV144 ALVAC-HIV vCP1521/AIDSVAX B/E vaccine trial, held in Thailand, resulted in an estimated 31.2% efficacy against HIV infection. By contrast, vaccination with VAX003 (consisting of only AIDSVAX B/E) was not protective. Because protection within RV144 was observed in the absence of neutralizing antibody activity or cytotoxic T cell responses, we speculated that the specificity or qualitative differences in Fc-effector profiles of nonneutralizing antibodies may have accounted for the efficacy differences observed between the two trials. We show that the RV144 regimen elicited nonneutralizing antibodies with highly coordinated Fc-mediated effector responses through the selective induction of highly functional immunoglobulin G3 (IgG3). By contrast, VAX003 elicited monofunctional antibody responses influenced by IgG4 selection, which was promoted by repeated AIDSVAX B/E protein boosts. Moreover, only RV144 induced IgG1 and IgG3 antibodies targeting the crown of the HIV envelope V2 loop, albeit with limited coverage of breakthrough viral sequences. These data suggest that subclass selection differences associated with coordinated humoral functional responses targeting strain-specific protective V2 loop epitopes may underlie differences in vaccine efficacy observed between these two vaccine trials.
ISSN: 19466242
Appears in Collections:Scopus 2011-2015

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