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Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design

Journal Article · · Nature Structural & Molecular Biology
DOI:https://doi.org/10.1038/nsmb.3144· OSTI ID:1238279
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  1. National Inst. of Health (NIH), Bethesda, MD (United States)
  2. Univ. of Washington, Seattle, WA (United States)
  3. National Inst. of Health (NIH), Bethesda, MD (United States); Univ. of Texas, Austin, TX (United States)
  4. Univ. of California, San Francisco, CA (United States)
  5. Univ. of Texas, Austin, TX (United States)
  6. National Human Genome Research Institute, NIH, Bethesda, MD (United States)
  7. Frederick National Lab. for Cancer Research, MD (United States)
  8. Duke Univ. Medical Center, Durham, NC (United States)
  9. National Inst. for Communicable Diseases of the National Health Lab. Service, Johannesburg (South Africa); Univ. of KwaZulu-Natal, Congella (South Africa)
  10. National Inst. for Communicable Diseases of the National Health Lab. Service, Johannesburg (South Africa); Univ. of the Witwatersrand, Johannesburg (South Africa); Univ. of KwaZulu-Natal, Congella (South Africa)
  11. National Inst. of Health (NIH), Bethesda, MD (United States); Columbia Univ., New York, NY (United States)
+ Show Author Affiliations
Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. As a result, the ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery; Frederick National Laboratory for Cancer Research; Intramural Research Program of the Vaccine Research Center; NIH; U.S. National Inst. of Allergy and Infectious Diseases (NIAID); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Grant/Contract Number:
W-31109-ENG-38
OSTI ID:
1238279
Journal Information:
Nature Structural & Molecular Biology, Journal Name: Nature Structural & Molecular Biology Journal Issue: 1 Vol. 23; ISSN 1545-9993
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth journal October 2018
V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity journal December 2018
The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template journal May 2019
HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design journal August 2019
HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage journal November 2017
Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies journal January 2016
Common helical V1V2 conformations of HIV-1 Envelope expose the α4β7 binding site on intact virions journal October 2018
Anti-idiotypic antibodies elicit anti-HIV-1–specific B cell responses journal July 2019
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Identification and specificity of broadly neutralizing antibodies against HIV journal January 2017
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Production of complex viral glycoproteins in plants as vaccine immunogens journal July 2018
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HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees journal January 2018
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Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage text January 2018

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60 APPLIED LIFE SCIENCES
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