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