Broad coverage of neutralization-resistant SIV strains by second-generation SIV-specific antibodies targeting the region involved in binding CD4.

Autor: Welles HC; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., King HAD; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America., Nettey L; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Cavett N; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Gorman J; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Zhou T; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Tsybovsky Y; Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Du R; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Song K; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Nguyen R; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Ambrozak D; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Ransier A; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Schramm CA; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Doria-Rose NA; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Swanstrom AE; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America., Hoxie JA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., LaBranche C; Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America., Montefiori DC; Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America., Douek DC; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Kwong PD; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Mascola JR; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Roederer M; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America., Mason RD; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Jun 16; Vol. 18 (6), pp. e1010574. Date of Electronic Publication: 2022 Jun 16 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010574
Abstrakt: Both SIV and SHIV are powerful tools for evaluating antibody-mediated prevention and treatment of HIV-1. However, owing to a lack of rhesus-derived SIV broadly neutralizing antibodies (bnAbs), testing of bnAbs for HIV-1 prevention or treatment has thus far been performed exclusively in the SHIV NHP model using bnAbs from HIV-1-infected individuals. Here we describe the isolation and characterization of multiple rhesus-derived SIV bnAbs capable of neutralizing most isolates of SIV. Eight antibodies belonging to two clonal families, ITS102 and ITS103, which target unique epitopes in the CD4 binding site (CD4bs) region, were found to be broadly neutralizing and together neutralized all SIV strains tested. A rare feature of these bnAbs and two additional antibody families, ITS92 and ITS101, which mediate strain-specific neutralizing activity against SIV from sooty mangabeys (SIVsm), was their ability to achieve near complete (i.e. 100%) neutralization of moderately and highly neutralization-resistant SIV. Overall, these newly identified SIV bnAbs highlight the potential for evaluating HIV-1 prophylactic and therapeutic interventions using fully simian, rhesus-derived bnAbs in the SIV NHP model, thereby circumventing issues related to rapid antibody clearance of human-derived antibodies, Fc mismatch and limited genetic diversity of SHIV compared to SIV.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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