Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
- Uniformed Services University of the Health Sciences, Bethesda, MD (United States). Dept. of Medicine Infectious Disease Division; Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States). School of Medicine. Division of Vaccine Research of Inst. of Human Virology; OSTI
- Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States). School of Medicine. Division of Vaccine Research of Inst. of Human Virology
- Uniformed Services University of the Health Sciences, Bethesda, MD (United States). Dept. of Medicine Infectious Disease Division; Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States). School of Medicine. Division of Vaccine Research of Inst. of Human Virology
- Duke Univ., Durham, NC (United States). Medical Center. Dept. of Surgery
- Uniformed Services University of the Health Sciences, Bethesda, MD (United States). Dept. of Medicine Infectious Disease Division
- Duke Univ., Durham, NC (United States). Duke Human Vaccine Inst. and Medical Center. Dept. of Medicine
- Duke Univ., Durham, NC (United States). Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine
- Duke Univ., Durham, NC (United States). Duke Human Vaccine Inst. and Medical Center. Dept. of Pediatrics
- Duke Univ., Durham, NC (United States). Medical Center. Dept. of Surgery, Duke Human Vaccine Inst., and Medical Center. Dept. of Molecular Genetics and Microbiology
Antibodies (Abs) specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (C1/C2) were induced in the RV144 vaccine trial, where antibody-dependent cellular cytotoxicity (ADCC) correlated with reduced risk of HIV-1 infection. We combined X-ray crystallography and fluorescence resonance energy transfer-fluorescence correlation spectroscopy to describe the molecular basis for epitopes of seven RV144 Abs and compared them to A32 and C11, C1/C2 Abs induced in HIV infection. Our data indicate that most vaccine Abs recognize the 7-stranded β-sandwich of gp120, a unique hybrid epitope bridging A32 and C11 binding sites. Although primarily directed at the 7-stranded β-sandwich, some accommodate the gp120 N terminus in C11-bound 8-stranded conformation and therefore recognize a broader range of CD4-triggered Env conformations. Our data also suggest that Abs of RV144 and RV305, the RV144 follow-up study, although likely initially induced by the ALVAC-HIV prime encoding full-length gp120, matured through boosting with truncated AIDSVAX gp120 variants.
- Research Organization:
- Stanford Univ., CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- Grant/Contract Number:
- AC02-76SF00515
- OSTI ID:
- 1816249
- Journal Information:
- mBio, Journal Name: mBio Journal Issue: 3 Vol. 11; ISSN 2161-2129
- Publisher:
- American Society for Microbiology (ASM)Copyright Statement
- Country of Publication:
- United States
- Language:
- English
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