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Title: A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope

Journal Article · · Immunity
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  1. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases (NIAID)
  2. Frederick National Lab. for Cancer Research, MD (United States)
  3. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases (NIAID); Vanderbilt Univ., Nashville, TN (United States)
  4. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases (NIAID) and National Inst. of Diabetes, Digestive and Kidney Diseases (NIDDK)
  5. Walter Reed Army Inst. of Research, Silver Spring, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD (United States)
  6. Rockefeller Univ., New York, NY (United States). Aaron Diamond AIDS Research Center
  7. Academia Sinica, Taipei (Taiwan)
  8. National Inst. of Health (NIH), Bethesda, MD (United States), National Human Genome Research Inst. (NHGRI)
  9. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Diabetes, Digestive and Kidney Diseases (NIDDK)
  10. The Scripps Research Inst., La Jolla, CA (United States); Ragon Inst., Cambridge, MA (United States)
  11. Walter Reed Army Inst. of Research, Silver Spring, MD (United States)
  12. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases (NIAID); Columbia Univ., New York, NY (United States)
  13. Academia Sinica, Taipei (Taiwan); The Scripps Research Inst., La Jolla, CA (United States)
  14. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases (NIAID); Rockefeller Univ., New York, NY (United States). Aaron Diamond AIDS Research Center
  15. NIH Intramural Sequencing Center (NISC), Bethesda, MD (United States). Comparative Sequencing Program
+ Show Author Affiliations

Virtually the entire surface of the HIV-1-envelope trimer is recognized by neutralizing antibodies, except for a highly glycosylated region at the center of the “silent face” on the gp120 subunit. From an HIV-1-infected donor, #74, we identified antibody VRC-PG05, which neutralized 27% of HIV-1 strains. The crystal structure of the antigen-binding fragment of VRC-PG05 in complex with gp120 revealed an epitope comprised primarily of N-linked glycans from N262, N295, and N448 at the silent face center. Furthermore, somatic hypermutation occurred preferentially at antibody residues that interacted with these glycans, suggesting somatic development of glycan recognition. Resistance to VRC-PG05 in donor #74 involved shifting of glycan-N448 to N446 or mutation of glycan-proximal residue E293. HIV-1 neutralization can thus be achieved at the silent face center by glycan-recognizing antibody; along with other known epitopes, the VRC-PG05 epitope completes coverage by neutralizing antibody of all major exposed regions of the prefusion closed trimer.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH); International AIDS Vaccine Initiative’s (IAVI’s) Neutralizing Antibody Consortium; Frederick National Laboratory for Cancer Research; USDOE Office of Science (SC), Basic Energy Sciences (BES); Academia Sinica; Ministry of Science and Technology
Contributing Organization:
NISC Comparative Sequencing Program
Grant/Contract Number:
R21 AI108399; HHSN261200800001E; W-31-109-Eng-38; R01 AI131722; 106-0210- 01-15-02; 104-0210-01-09-02; 103-2321-B-001-004; R01 AI072155
OSTI ID:
1506497
Journal Information:
Immunity, Vol. 48, Issue 3; ISSN 1074-7613
Publisher:
Cell PressCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 54 works
Citation information provided by
Web of Science

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Cited By (9)

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Recent progress in broadly neutralizing antibodies to HIV journal October 2018
Mapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines journal March 2020
Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope journal June 2019
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability journal November 2019
Protein and Glycan Mimicry in HIV Vaccine Design journal May 2019

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59 BASIC BIOLOGICAL SCIENCES
broadly neutralizing antibody
crystal structure
glycan cluster
glycan recognition
glycopeptide epitope
HIV silent face
HIV vaccine
prefusion-closed Env trimer
viral escape