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Title: IgG3 collaborates with IgG1 and IgA to recruit effector function in RV144 vaccinees
Authors: Stephanie Fischinger
Sepideh Dolatshahi
Madeleine F. Jennewein
Supachai Rerks-Ngarm
Punnee Pitisuttithum
Sorachai Nitayaphan
Nelson Michael
Sandhya Vasan
Margaret E. Ackerman
Hendrik Streeck
Galit Alter
Universitäts-Klinikum Bonn und Medizinische Fakultät
Thayer School of Engineering at Dartmouth
Massachusetts Institute of Technology
University of Virginia
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Universität Duisburg-Essen
Walter Reed Army Institute of Research
Mahidol University
Keywords: Medicine
Issue Date: 5-Nov-2020
Citation: JCI Insight. Vol.5, No.21 (2020)
Abstract: Copyright: © 2020, Fischinger et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. While the RV144 HIV vaccine trial led to moderately reduced risk of HIV acquisition, emerging data from the HVTN702 trial point to the critical need to reexamine RV144-based correlates of reduced risk of protection. While in RV144, the induction of V2-binding, non-IgA, IgG3 antibody responses with nonneutralizing functions were linked to reduced risk of infection, the interactions between these signatures remain unclear. Thus, here we comprehensively profile the humoral immune response in 300 RV144 vaccinees to decipher the relationships between humoral biomarkers of protection. We found that vaccine-specific IgG1, IgG3, and IgA were highly correlated. However, ratios of IgG1:IgG3:IgA provided insights into subclass/isotype polyclonal functional regulation. For instance, in the absence of high IgG1 levels, IgG3 antibodies exhibited limited functional activity, pointing to IgG3 as a critical contributor, but not sole driver, of effective antiviral humoral immunity. Higher IgA levels were linked to enhanced antibody effector function, including neutrophil phagocytosis (ADNP), complement deposition (ADCD), and antibody-dependent NK degranulation (CD107a), some of which were increased in infected vaccinees in a case/control data set, suggesting that IgA-driven functions compromised immunity. These data highlight the interplay between IgG1, IgG3, and IgA, pointing to the need to profile the relationships between subclass/isotype selection.
ISSN: 23793708
Appears in Collections:Scopus 2020

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