Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine
Dapeng Li, David R. Martinez, Alexandra Schäfer, Haiyan Chen, Maggie Barr, Laura L. Sutherland, Esther Lee, Robert Parks, Dieter Mielke, W. Daniel Edwards, Amanda Newman, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Matthew Gagné, Daniel C. Douek, C. Todd DeMarco, Thomas N. Denny, Thomas H. Oguin, Alecia Brown, Wes Rountree, Yunfei Wang, Katayoun Mansouri, Robert J. Edwards, Guido Ferrari, Gregory D. Sempowski, Amanda Eaton, Juanjie Tang, Derek W. Cain, Sampa Santra, Norbert Pardi, Drew Weissman, Mark A. Tomai, Christopher B. Fox, Ian N. Moore, Hanné Andersen, Mark G. Lewis, Hana Golding, Robert A. Seder, Surender Khurana, Ralph S. Baric, David C. Montefiori, Kevin O. Saunders, Barton F. Haynes
Abstract
Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants.