Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response
Year: 2025
Type: article
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.
Source: Nature Communications
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
Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, University of Massachusetts Chan Medical School, Scripps Research Institute, Vaccine Research Center, International AIDS Vaccine Initiative
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4410980468