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HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope

Author

Listed:
  • Daniela Fera

    (Harvard Medical School)

  • Matthew S. Lee

    (Harvard Medical School)

  • Kevin Wiehe

    (Duke University Medical Center
    Duke Human Vaccine Institute)

  • R. Ryan Meyerhoff

    (Duke Human Vaccine Institute
    Duke University Medical Center)

  • Alessandro Piai

    (Harvard Medical School)

  • Mattia Bonsignori

    (Duke University Medical Center
    Duke Human Vaccine Institute)

  • Baptiste Aussedat

    (Sloan Kettering Institute)

  • William E. Walkowicz

    (Sloan Kettering Institute)

  • Therese Ton

    (Swarthmore College)

  • Jeffrey O. Zhou

    (Swarthmore College)

  • Samuel Danishefsky

    (Sloan Kettering Institute)

  • Barton F. Haynes

    (Duke University Medical Center
    Duke Human Vaccine Institute)

  • Stephen C. Harrison

    (Harvard Medical School
    Harvard Medical School)

Abstract

HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide (“Man9-V3”) for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage (“DH270”), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs—the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen.

Suggested Citation

  • Daniela Fera & Matthew S. Lee & Kevin Wiehe & R. Ryan Meyerhoff & Alessandro Piai & Mattia Bonsignori & Baptiste Aussedat & William E. Walkowicz & Therese Ton & Jeffrey O. Zhou & Samuel Danishefsky & , 2018. "HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03565-6
    DOI: 10.1038/s41467-018-03565-6
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    Cited by:

    1. Rory Henderson & Ye Zhou & Victoria Stalls & Kevin Wiehe & Kevin O. Saunders & Kshitij Wagh & Kara Anasti & Maggie Barr & Robert Parks & S. Munir Alam & Bette Korber & Barton F. Haynes & Alberto Barte, 2023. "Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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