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
Moliva, J. I.; Andrew, S. F.; Flynn, B. J.; Wagner, D. A.; Foulds, K. E.; Gagne, M.; Flebbe, D. R.; Lamb, E.; Provost, S.; Marquez, J.; Mychalowych, A.; Lorag, C.; Honeycutt, C. C.; Burnett, M. R.; McCormick, L.; Henry, A. R.; Godbole, S.; Davis-Gardner, M. E.; Minai, M.; Bok, K. W.; Nagata, B. M.; Todd, J.-P. M.; McCarthy, E.; Dodson, A.; Kouneski, K.; Cook, A.; Pessaint, L.; Van Ry, A.; Valentin, D.; Young, S.; Littman, Y.; Boon, A. C. M.; Suthar, M. S.; Lewis, M. G.; Andersen, H.; Alves, D. A.; Woodward, R.; Leuzzi, A.; Vitelli, A.; Colloca, S.; Folgori, A.; Raggiolli, A.; Capone, S.; Nason
Show 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, theres 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.
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