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Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity

Author

Listed:
  • Ralph Pantophlet

    (Simon Fraser University
    Simon Fraser University
    Simon Fraser University)

  • Nino Trattnig

    (University of Natural Resources and Life Sciences)

  • Sasha Murrell

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Naiomi Lu

    (Simon Fraser University)

  • Dennis Chau

    (Simon Fraser University)

  • Caitlin Rempel

    (Simon Fraser University)

  • Ian A. Wilson

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Paul Kosma

    (University of Natural Resources and Life Sciences)

Abstract

Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1.

Suggested Citation

  • Ralph Pantophlet & Nino Trattnig & Sasha Murrell & Naiomi Lu & Dennis Chau & Caitlin Rempel & Ian A. Wilson & Paul Kosma, 2017. "Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01640-y
    DOI: 10.1038/s41467-017-01640-y
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    Cited by:

    1. Rory Henderson & Kara Anasti & Kartik Manne & Victoria Stalls & Carrie Saunders & Yishak Bililign & Ashliegh Williams & Pimthada Bubphamala & Maya Montani & Sangita Kachhap & Jingjing Li & Chuancang J, 2024. "Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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