Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response
- 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
2025-06-03
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.