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Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response

Author

Listed:
  • Kenta Matsuda

    (National Institutes of Health)

  • Mitra Harrison

    (National Institutes of Health)

  • Eleanor Wettstein

    (National Institutes of Health)

  • Jessica Pederson

    (National Institutes of Health)

  • Alyssa A. Pullano

    (National Institutes of Health)

  • Lyuba Bolkhovitinov

    (National Institutes of Health)

  • Breanna Kim

    (National Institutes of Health)

  • Isabel Steinberg

    (National Institutes of Health)

  • Trevor Griesman

    (National Institutes of Health)

  • Sarah Stuccio

    (National Institutes of Health)

  • Daniel Rogan

    (National Institutes of Health)

  • Andy Patamawenu

    (National Institutes of Health)

  • Tulley Shofner

    (National Institutes of Health)

  • Nathaniel E. Wright

    (National Institutes of Health)

  • Jonathan D. Webber

    (National Institutes of Health)

  • Freya van’t Veer

    (National Institutes of Health)

  • Rachel Roenicke

    (National Institutes of Health)

  • Emma Koory

    (National Institutes of Health)

  • Peyton M. Roeder

    (National Institutes of Health)

  • Ellison Ober

    (National Institutes of Health)

  • Benjamin Leach

    (National Institutes of Health)

  • Yaroslav Tsybovsky

    (Frederick National Laboratory for Cancer Research)

  • Tyler Stephens

    (Frederick National Laboratory for Cancer Research)

  • Ivan Moral-Sanchez

    (University of Amsterdam)

  • Ilja Bontjer

    (University of Amsterdam)

  • Lori W. McGinnes-Cullen

    (University of Massachusetts Medical School)

  • Eric Chu

    (National Institutes of Health)

  • Jason Liang

    (National Institutes of Health)

  • Jonathan L. Torres

    (The Scripps Research Institute)

  • Ryan N. Lin

    (The Scripps Research Institute)

  • Andy S. Tran

    (The Scripps Research Institute)

  • Gabrielle Dziubla

    (National Institutes of Health)

  • Leonid Serebryannyy

    (National Institutes of Health)

  • Sandeep Narpala

    (National Institutes of Health)

  • Bob Lin

    (National Institutes of Health)

  • Mike Castro

    (National Institutes of Health)

  • Gabriel Ozorowski

    (The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute)

  • Rogier W. Sanders

    (University of Amsterdam)

  • Peter D. Kwong

    (National Institutes of Health)

  • Javier Guenaga

    (The Scripps Research Institute)

  • Richard Wyatt

    (The Scripps Research Institute)

  • Trudy Morrison

    (University of Massachusetts Medical School)

  • Mark Connors

    (National Institutes of Health)

Abstract

HIV-1 Env glycoprotein (Env) immunogenicity is limited in part by structural instability and extensive glycan shielding and is likely the greatest obstacle to an HIV-1 vaccine. Stabilized Env trimers can elicit serum neutralizing antibodies, but the response is short-lived. Here we use Newcastle Disease Virus-like particle (NDV-VLP) platform to present stabilized versions of HIV-1 Env at high valency and in the context of varied conformational stability, adjuvants, dose, and antigen persistence. Influenza virus hemagglutinin, or SARS-CoV2 Spike-bearing VLPs rapidly induce neutralizing antibodies, in contrast, they were not induced by those bearing Env. A replicating adenovirus type 4 expressing Env rapidly induces autologous neutralizing antibodies. However, durable neutralizing antibodies are induced only when multiple features of a replicating virus infection are combined, with the largest impact from dose and escalating dose. In summary, we show here immunogenicity of HIV-1 Env could be improved by reproducing features of virus infection.

Suggested Citation

  • Kenta Matsuda & Mitra Harrison & Eleanor Wettstein & Jessica Pederson & Alyssa A. Pullano & Lyuba Bolkhovitinov & Breanna Kim & Isabel Steinberg & Trevor Griesman & Sarah Stuccio & Daniel Rogan & Andy, 2025. "Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60481-2
    DOI: 10.1038/s41467-025-60481-2
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