National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01 AI157299
United States
Citation
Journal: Nat Commun / Year: 2025 Title: Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response. Authors: Kenta Matsuda / Mitra Harrison / Eleanor Wettstein / Jessica Pederson / Alyssa A Pullano / Lyuba Bolkhovitinov / Breanna Kim / Isabel Steinberg / Trevor Griesman / Sarah Stuccio / Daniel ...Authors: 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 / 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 ...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.
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