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Title: HIV vaccine delayed boosting increases Env variable region 2–specific antibody effector functions
Authors: David Easterhoff
Justin Pollara
Kan Luo
Benjamin Janus
Neelakshi Gohain
La Tonya D. Williams
Matthew Zirui Tay
Anthony Monroe
Kristina Peachman
Misook Choe
Susie Min
Paolo Lusso
Peng Zhang
Eden P. Go
Heather Desaire
Mattia Bonsignori
Kwan Ki Hwang
Charles Beck
Matina Kakalis
Robert J. O’Connell
Sandhya Vasan
Jerome H. Kim
Nelson L. Michael
Jean Louis Excler
Merlin L. Robb
Supachai Rerks-Ngarm
Jaranit Kaewkungwal
Punnee Pitisuttithum
Sorachai Nitayaphan
Faruk Sinangil
James Tartaglia
Sanjay Phogat
Kevin Wiehe
Kevin O. Saunders
David C. Montefiori
Georgia D. Tomaras
M. Anthony Moody
James Arthos
Mangala Rao
M. Gordon Joyce
Gilad Ofek
Guido Ferrari
Barton F. Haynes
Duke University Medical Center
GlaxoSmithKline SpA
International Vaccine Institute, Seoul
Sanofi Pasteur SA
National Institute of Allergy and Infectious Diseases
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
University of Kansas, Lawrence
Walter Reed Army Institute of Research
Mahidol University
Duke University School of Medicine
University of Maryland
Health Policy
Global Solutions for Infectious Diseases
Keywords: Medicine
Issue Date: 30-Jan-2020
Citation: JCI Insight. Vol.5, No.2 (2020)
Abstract: © 2020, American Society for Clinical Investigation. In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2–specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope–specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti–HIV-1 effector functions.
ISSN: 23793708
Appears in Collections:Scopus 2020

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