Frontiers in Immunology (Dec 2021)
Polyclonal Broadly Neutralizing Antibody Activity Characterized by CD4 Binding Site and V3-Glycan Antibodies in a Subset of HIV-1 Virus Controllers
- Tinashe E. Nyanhete,
- Tinashe E. Nyanhete,
- Tinashe E. Nyanhete,
- Robert J. Edwards,
- Robert J. Edwards,
- Celia C. LaBranche,
- Katayoun Mansouri,
- Amanda Eaton,
- S. Moses Dennison,
- S. Moses Dennison,
- S. Moses Dennison,
- Kevin O. Saunders,
- Kevin O. Saunders,
- Derrick Goodman,
- Derrick Goodman,
- Derrick Goodman,
- Katarzyna Janowska,
- Rachel L. Spreng,
- Rachel L. Spreng,
- Rachel L. Spreng,
- Lu Zhang,
- Lu Zhang,
- Lu Zhang,
- Sarah V. Mudrak,
- Sarah V. Mudrak,
- Sarah V. Mudrak,
- Thomas J. Hope,
- Bhavna Hora,
- Bhavna Hora,
- Todd Bradley,
- Todd Bradley,
- Ivelin S. Georgiev,
- David C. Montefiori,
- David C. Montefiori,
- Priyamvada Acharya,
- Priyamvada Acharya,
- Georgia D. Tomaras,
- Georgia D. Tomaras,
- Georgia D. Tomaras,
- Georgia D. Tomaras,
- Georgia D. Tomaras
Affiliations
- Tinashe E. Nyanhete
- Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, United States
- Tinashe E. Nyanhete
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Tinashe E. Nyanhete
- Department of Immunology, Duke University School of Medicine, Durham, NC, United States
- Robert J. Edwards
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Robert J. Edwards
- Department of Medicine, Duke University School of Medicine, Durham, NC, United States
- Celia C. LaBranche
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Katayoun Mansouri
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Amanda Eaton
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- S. Moses Dennison
- Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, United States
- S. Moses Dennison
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- S. Moses Dennison
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Kevin O. Saunders
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Kevin O. Saunders
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Derrick Goodman
- Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, United States
- Derrick Goodman
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Derrick Goodman
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Katarzyna Janowska
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Rachel L. Spreng
- Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, United States
- Rachel L. Spreng
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Rachel L. Spreng
- Department of Medicine, Duke University School of Medicine, Durham, NC, United States
- Lu Zhang
- Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, United States
- Lu Zhang
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Lu Zhang
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Sarah V. Mudrak
- Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, United States
- Sarah V. Mudrak
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Sarah V. Mudrak
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Thomas J. Hope
- Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
- Bhavna Hora
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Bhavna Hora
- Department of Medicine, Duke University School of Medicine, Durham, NC, United States
- Todd Bradley
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Todd Bradley
- Department of Medicine, Duke University School of Medicine, Durham, NC, United States
- Ivelin S. Georgiev
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, United States
- David C. Montefiori
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- David C. Montefiori
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Priyamvada Acharya
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Priyamvada Acharya
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Georgia D. Tomaras
- Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, United States
- Georgia D. Tomaras
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States
- Georgia D. Tomaras
- Department of Immunology, Duke University School of Medicine, Durham, NC, United States
- Georgia D. Tomaras
- Department of Surgery, Duke University School of Medicine, Durham, NC, United States
- Georgia D. Tomaras
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.670561
- Journal volume & issue
-
Vol. 12
Abstract
Broadly neutralizing antibodies (bNAbs), known to mediate immune control of HIV-1 infection, only develop in a small subset of HIV-1 infected individuals. Despite being traditionally associated with patients with high viral loads, bNAbs have also been observed in therapy naïve HIV-1+ patients naturally controlling virus replication [Virus Controllers (VCs)]. Thus, dissecting the bNAb response in VCs will provide key information about what constitutes an effective humoral response to natural HIV-1 infection. In this study, we identified a polyclonal bNAb response to natural HIV-1 infection targeting CD4 binding site (CD4bs), V3-glycan, gp120-gp41 interface and membrane-proximal external region (MPER) epitopes on the HIV-1 envelope (Env). The polyclonal antiviral antibody (Ab) response also included antibody-dependent cellular phagocytosis of clade AE, B and C viruses, consistent with both the Fv and Fc domain contributing to function. Sequence analysis of envs from one of the VCs revealed features consistent with potential immune pressure and virus escape from V3-glycan targeting bNAbs. Epitope mapping of the polyclonal bNAb response in VCs with bNAb activity highlighted the presence of gp120-gp41 interface and CD4bs antibody classes with similar binding profiles to known potent bNAbs. Thus, these findings reveal the induction of a broad and polyfunctional humoral response in VCs in response to natural HIV-1 infection.
Keywords
- HIV-1 Virus Controllers
- broadly neutralizing antibodies
- antibody-dependent cellular phagocytosis (ADCP)
- CD4-binding site antibodies
- negative-stain electron microscopy
- neutralization fingerprinting assay
