Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates

Erasmus, Jesse H.; Khandhar, Amit P.; Walls, Alexandra C.; Hemann, Emily A.; O’Connor, Megan A.; Murapa, Patience; Archer, Jacob; Leventhal, Shanna; Fuller, Jim; Lewis, Thomas; Draves, Kevin E.; Randall, Samantha; Guerriero, Kathryn A.; Duthie, Malcolm S.; Carter, Darrick; Reed, Steven G.; Hawman, David W.; Feldmann, Heinz; Gale, Michael; Veesler, David; Berglund, Peter; Fuller, Deborah Heydenburg

The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.