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TitleAntigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 5162, Year 2025
Publish dateJun 3, 2025
AuthorsKenta 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 /
PubMed AbstractHIV-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 ...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.
External linksNat Commun / PubMed:40461490 / PubMed Central
MethodsEM (single particle)
Resolution15.0 Å
Structure data

EMDB-49656: Rabbit RB142 polyclonal Fab in complex with HIV-1 1086C NFL Env trimer
Method: EM (single particle) / Resolution: 15.0 Å

Source
  • Oryctolagus cuniculus (rabbit)

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