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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月3日

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  • Kenta Matsuda,
  • Mitra Harrison,
  • Eleanor Wettstein,
  • Jessica Pederson,
  • Alyssa A. Pullano,
  • Lyuba Bolkhovitinov,
  • Breanna Kim,
  • Isabel Steinberg,
  • Trevor Griesman,
  • Sarah Stuccio,
  • Daniel Rogan,
  • Andy Patamawenu,
  • Tulley Shofner,
  • Nathaniel E. Wright,
  • Jonathan D. Webber,
  • Freya van’t Veer,
  • Rachel Roenicke,
  • Emma Koory,
  • Peyton M. Roeder,
  • Ellison Ober,
  • Benjamin Leach,
  • Yaroslav Tsybovsky,
  • Tyler Stephens,
  • Ivan Del Moral-Sanchez,
  • Ilja Bontjer,
  • Lori W. McGinnes-Cullen,
  • Eric Chu,
  • Jason Liang,
  • Jonathan L. Torres,
  • Ryan N. Lin,
  • Andy S. Tran,
  • Gabrielle Dziubla,
  • Leonid Serebryannyy,
  • Sandeep Narpala,
  • Bob Lin,
  • Mike Castro,
  • Gabriel Ozorowski,
  • Andrew B. Ward,
  • Rogier W. Sanders,
  • Peter D. Kwong,
  • Javier Guenaga,
  • Richard Wyatt,
  • Trudy Morrison,
  • Mark Connors

摘要

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.