Publication

VH1-69 Utilizing Antibodies Are Capable of Mediating Non-neutralizing Fc-Mediated Effector Functions Against the Transmitted/Founder gp120

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Last modified
  • 05/21/2025
Type of Material
Authors
    S. Abigail Smith, Emory UniversitySamantha L. Burton, Emory UniversityWilliam Kilembe, Zambia Emory HIV Research ProjectShabir Lakhi, Zambia Emory HIV Research ProjectEtienne Karita, Projet San FranciscoMatt Price, University of California San FranciscoSusan Allen, Emory UniversityCynthia Derdeyn, Emory University
Language
  • English
Date
  • 2019-01-15
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2019 Smith, Burton, Kilembe, Lakhi, Karita, Price, Allen and Derdeyn.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-3224
Volume
  • 9
Start Page
  • 3163
End Page
  • 3163
Grant/Funding Information
  • This work was facilitated by the Emory Vaccine Center Flow Core of the Center for AIDS Research at Emory University (P30AI050409).
  • This study was made possible through samples and data collected as part of the Zambia-Emory HIV Research Project (ZEHRP), Project San Francisco (PSF), the Rwanda Zambia HIV Research Group (RZHRG) at Emory University, and the International AIDS Vaccine Initiative (IAVI) Protocol C Research Network.
  • This study was funded by NIH R01 AI-58706 (CD) and NIH R01 AI-128837 (CD).
  • This work was funded in part by IAVI and made possible by the support of many donors, including United States Agency for International Development (USAID).
Supplemental Material (URL)
Abstract
  • Multiple antibody effector functions arise in HIV-1 infection that could be harnessed to protect against infection or clear the persistent reservoir. Here, we have investigated the genetic and functional memory B cell and antibody landscape present during early infection in six individuals infected with either subtype A, C, or an A/C recombinant HIV-1. These individuals demonstrated varying levels of plasma autologous neutralization (nAb) against the transmitted/founder envelope (T/F Env) pseudovirus and non-neutralizing Fc-mediated effector function (nnFc) antibody-dependent cell-mediated cytotoxicity (ADCC) against the T/F Env gp120 protein at ~7 months after infection. Genetic analysis of the immunoglobulin heavy (VH) and light (VL) chain variable domain gene segments from 352 autologous T/F Env gp120-specific single B cells recovered at this same 7-month time-point revealed an over-representation of the VH1-69 germline in five of six individuals. A defining feature of the VH1-69 utilizing gp120-specific antibodies was their significantly more hydrophobic complementarity-determining region-2 (CDRH2) regions compared to other VH CDRH2 sequences from each individual. While none of the VH1-69 antibodies possessed strong neutralizing activity against virions pseudotyped with the autologous T/F Env, almost a third were capable of mediating high ADCC activity, as assayed by intracellular granzyme B activity in CEM.NKr.CCR5 target cells coated with autologous T/F Env gp120. High ADCC mediating VH1-69 antibodies exhibited shorter complementarity-determining region-3 (CDRH3) lengths and a more neutral isoelectric point than antibodies lacking this function. In the individual that developed the highest autologous ADCC responses, the high granzyme B producing antibodies bound to surface expressed envelope in the absence of CD4 and were not enhanced by the addition of soluble CD4. Overall, VH1-69 utilizing antibodies are commonly induced against gp120 in diverse HIV-1 infections and a subset of these antibodies can mediate ADCC functions, serving as a bridge between the innate and adaptive immune response to HIV-1.
Author Notes
Keywords
Research Categories
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • Health Sciences, Immunology

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