Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response
Abstract
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.
Article Details
Authors (44)
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
Department of Integrative Structural and Computational Biology, The Scripps Research Institute
Ryan N. Lin
Andy S. Tran
Gabrielle Dziubla
Leonid Serebryannyy
Sandeep Narpala
Bob Lin
Mike Castro
Gabriel Ozorowski
Andrew B. Ward
Rogier W. Sanders
Department of Medical Microbiology and Infection Prevention, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam
Peter D. Kwong
Javier Guenaga
Richard Wyatt
Trudy Morrison
Mark Connors