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
Author:
Moliva Juan I., Andrew Shayne F., Flynn Barbara J., Wagner Danielle A., Foulds Kathryn E., Gagne Matthew, Flebbe Dillon R., Lamb Evan, Provost Samantha, Marquez Josue, Mychalowych Anna, Lorag Cynthia G., Honeycutt Christopher Cole, Burnett Matthew R., McCormick Lauren, Henry Amy R., Godbole Sucheta, Davis-Gardner Meredith E.ORCID, Minai Mahnaz, Bock Kevin W., Nagata Bianca M., Todd John-Paul M., McCarthy Elizabeth, Dodson Alan, Kouneski Katelyn, Cook Anthony, Pessaint Laurent, Van Ry Alex, Valentin Daniel, Young Steve, Littman Yoav, Boon Adrianus C. M., Suthar Mehul S.ORCID, Lewis Mark G., Andersen Hanne, Alves Derron A., Woodward Ruth, Leuzzi Adriano, Vitelli Alessandra, Colloca Stefano, Folgori Antonella, Raggiolli Angelo, Capone StefaniaORCID, Nason Martha C., Douek Daniel C., Roederer Mario, Seder Robert A., Sullivan Nancy J.
Abstract
SummarySARS-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.
Publisher
Cold Spring Harbor Laboratory
|
|