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Polyclonal Broadly Neutralizing Antibody Activity Characterized by CD4 Binding Site and V3-Glycan Antibodies in a Subset of HIV-1 Virus Controllers.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Dec 23; Vol. 12, pp. 670561. Date of Electronic Publication: 2021 Dec 23 (Print Publication: 2021). - Publication Year :
- 2021
-
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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Nyanhete, Edwards, LaBranche, Mansouri, Eaton, Dennison, Saunders, Goodman, Janowska, Spreng, Zhang, Mudrak, Hope, Hora, Bradley, Georgiev, Montefiori, Acharya and Tomaras.)
- Subjects :
- Antibody Specificity
Binding Sites, Antibody
CD4 Antigens metabolism
CD4 Lymphocyte Count
Epitope Mapping
Female
Genes, env
HLA-B Antigens immunology
Humans
Immune Evasion
Immunoglobulin Fc Fragments immunology
Immunoglobulin Fragments immunology
Male
Models, Molecular
Phagocytosis
Protein Domains
Recombinant Proteins immunology
Viral Load
Broadly Neutralizing Antibodies immunology
CD4 Antigens immunology
Epitopes immunology
HIV Antibodies immunology
HIV Envelope Protein gp120 immunology
HIV Infections immunology
HIV-1 immunology
Peptide Fragments immunology
Survivors
Viremia immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 35003053
- Full Text :
- https://doi.org/10.3389/fimmu.2021.670561