Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates
Year: 2023
Type: preprint
Abstract: SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.5 variant of SARS-CoV-2. A prime-boost regimen using GRAd followed by adjuvanted S-2P (GRAd+S-2P) accelerated viral clearance in both the lower and upper airways. GRAd delivered via aerosol (GRAd(AE)+S-2P) modestly improved protection compared to its matched intramuscular regimen, but showed dramatically superior boosting by mRNA and, importantly, total virus clearance in the upper airway by day 4 post infection. GrAd vaccination regimens elicited robust and durable systemic and mucosal antibody responses to multiple SARS-CoV-2 variants, but only GRAd(AE)+S-2P generated long-lasting T cell responses in the lung. This research underscores the flexibility of the GRAd vaccine platform to provide durable immunity against SARS-CoV-2 in both the lower and upper airways.
Authors: Juan I. Moliva, Shayne F. Andrew, Barbara J. Flynn, Danielle A. Wagner, Kathryn E. Foulds, Matthew Gagne, Dillon R. Flebbe, Evan Lamb, Samantha Provost, Josue Marquez, Anna Mychalowych, Cynthia G. Lorag, Christopher Cole Honeycutt, Matthew R. Burnett, Lauren McCormick, Amy R. Henry, Sucheta Godbole, Meredith E. Davis-Gardner, Mahnaz Minai, Kevin W. Bock, Bianca M. Nagata, John-Paul M. Todd, Elizabeth McCarthy, Alan Dodson, Katelyn Kouneski, Anthony Cook, Laurent Pessaint, Alex Van Ry, Daniel Valentin, Steve Young, Yoav Littman, Adrianus C. M. Boon, Mehul S. Suthar, Mark G. Lewis, Hanne Andersen, Derron A. Alves, Ruth Woodward, Adriano Leuzzi, Alessandra Vitelli, Stefano Colloca, Antonella Folgori, Angelo Raggiolli, Stefania Capone, Martha C. Nason, Daniel C. Douek, Mario Roederer, Robert A. Seder, Nancy J. Sullivan
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4388923541