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Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial

Journal Article · · mBio
 [1];  [2];  [3];  [4];  [2];  [5];  [4];  [6];  [6];  [7];  [8];  [2];  [9];  [2];  [3]
  1. 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
  2. Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States). School of Medicine. Division of Vaccine Research of Inst. of Human Virology
  3. 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
  4. Duke Univ., Durham, NC (United States). Medical Center. Dept. of Surgery
  5. Uniformed Services University of the Health Sciences, Bethesda, MD (United States). Dept. of Medicine Infectious Disease Division
  6. Duke Univ., Durham, NC (United States). Duke Human Vaccine Inst. and Medical Center. Dept. of Medicine
  7. Duke Univ., Durham, NC (United States). Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine
  8. Duke Univ., Durham, NC (United States). Duke Human Vaccine Inst. and Medical Center. Dept. of Pediatrics
  9. 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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