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Title: Boosting with AIDSvax B/E enhances Env constant region 1 and 2 antibody-dependent cellular cytotoxicity breadth and potency
Authors: David Easterhoff
Justin Pollara
Kan Luo
William D. Tolbert
Brianna Young
Dieter Mielke
Shalini Jha
Robert J. O’Connell
Sandhya Vasan
Jerome 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
Thomas B. Kepler
S. Munir Alam
Kevin Wiehe
Kevin O. Saunders
David C. Montefiori
Georgia D. Tomaras
M. Anthony Moody
Marzena Pazgier
Barton F. Haynes
Guido Ferrari
GlaxoSmithKline SpA
International Vaccine Institute, Seoul
Sanofi Pasteur SA
Boston University
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
University of Maryland, Baltimore
Walter Reed Army Institute of Research
Mahidol University
Duke University
Uniformed Services University of the Health Sciences
Global Solutions for Infectious Diseases
Keywords: Agricultural and Biological Sciences;Immunology and Microbiology
Issue Date: 1-Feb-2020
Citation: Journal of Virology. Vol.94, No.4 (2020)
Abstract: © 2020 Easterhoff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Induction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce nonneutralizing antibodies (NNAbs) that kill virus-infected cells, as these antibody specificities have been implicated in slowing HIV-1 disease progression and in protection. HIV-1 Env constant region 1 and 2 (C1C2) monoclonal antibodies (MAbs) frequently mediate potent antibody-dependent cellular cytotoxicity (ADCC), making them an important vaccine target. Here, we explore the effect of delayed and repetitive boosting of RV144 vaccine recipients with AIDSVAX B/E on the C1C2-specific MAb repertoire. It was found that boosting increased clonal lineage-specific ADCC breadth and potency. A ligand crystal structure of a vaccine-induced broad and potent ADCC-mediating C1C2-specific MAb showed that it bound a highly conserved Env gp120 epitope. Thus, boosting to affinity mature these types of IgG C1C2-specific antibody responses may be one method by which to make an improved HIV vaccine with higher efficacy than that seen in the RV144 trial. IMPORTANCE Over one million people become infected with HIV-1 each year, making the development of an efficacious HIV-1 vaccine an important unmet medical need. The RV144 human HIV-1 vaccine regimen is the only HIV-1 clinical trial to date to demonstrate vaccine efficacy. An area of focus has been on identifying ways by which to improve upon RV144 vaccine efficacy. The RV305 HIV-1 vaccine regimen was a follow-up boost of RV144 vaccine recipients that occurred 6 to 8 years after the conclusion of RV144. Our study focused on the effect of delayed boosting in humans on the vaccine-induced Env constant region 1 and 2 (C1C2)-specific antibody repertoire. It was found that boosting with an HIV-1 Env vaccine increased C1C2-specific antibody-dependent cellular cytotoxicity potency and breadth.
ISSN: 10985514
Appears in Collections:Scopus 2020

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