tetano
Editor, Senior Moderator
Sci Transl Med
. 2020 Jul 20;eabc9396.
doi: 10.1126/scitranslmed.abc9396. Online ahead of print.
An alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates
Jesse H Erasmus[SUP] 1 2 [/SUP], Amit P Khandhar[SUP] 2 3 [/SUP], Megan A O'Connor[SUP] 1 4 [/SUP], Alexandra C Walls[SUP] 5 [/SUP], Emily A Hemann[SUP] 6 7 [/SUP], Patience Murapa[SUP] 1 [/SUP], Jacob Archer[SUP] 1 3 [/SUP], Shanna Leventhal[SUP] 8 [/SUP], James T Fuller[SUP] 1 [/SUP], Thomas B Lewis[SUP] 1 4 [/SUP], Kevin E Draves[SUP] 1 [/SUP], Samantha Randall[SUP] 1 [/SUP], Kathryn A Guerriero[SUP] 4 [/SUP], Malcolm S Duthie[SUP] 2 [/SUP], Darrick Carter[SUP] 2 3 6 [/SUP], Steven G Reed[SUP] 2 6 [/SUP], David W Hawman[SUP] 8 [/SUP], Heinz Feldmann[SUP] 8 [/SUP], Michael Gale Jr[SUP] 6 4 7 [/SUP], David Veesler[SUP] 5 [/SUP], Peter Berglund[SUP] 2 [/SUP], Deborah Heydenburg Fuller[SUP] 9 6 4 [/SUP]
Affiliations
Abstract
The COVID-19 pandemic, caused by infection with the SARS-CoV-2 coronavirus, is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale-up. Here, we developed an alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with Lipid InOrganic Nanoparticles (LION) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti-SARS-CoV-2 S protein IgG antibody isotypes indicative of a Type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in lung and spleen. Prime-only immunization of aged (17-month old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. Importantly, in nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in 5 intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.
. 2020 Jul 20;eabc9396.
doi: 10.1126/scitranslmed.abc9396. Online ahead of print.
An alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates
Jesse H Erasmus[SUP] 1 2 [/SUP], Amit P Khandhar[SUP] 2 3 [/SUP], Megan A O'Connor[SUP] 1 4 [/SUP], Alexandra C Walls[SUP] 5 [/SUP], Emily A Hemann[SUP] 6 7 [/SUP], Patience Murapa[SUP] 1 [/SUP], Jacob Archer[SUP] 1 3 [/SUP], Shanna Leventhal[SUP] 8 [/SUP], James T Fuller[SUP] 1 [/SUP], Thomas B Lewis[SUP] 1 4 [/SUP], Kevin E Draves[SUP] 1 [/SUP], Samantha Randall[SUP] 1 [/SUP], Kathryn A Guerriero[SUP] 4 [/SUP], Malcolm S Duthie[SUP] 2 [/SUP], Darrick Carter[SUP] 2 3 6 [/SUP], Steven G Reed[SUP] 2 6 [/SUP], David W Hawman[SUP] 8 [/SUP], Heinz Feldmann[SUP] 8 [/SUP], Michael Gale Jr[SUP] 6 4 7 [/SUP], David Veesler[SUP] 5 [/SUP], Peter Berglund[SUP] 2 [/SUP], Deborah Heydenburg Fuller[SUP] 9 6 4 [/SUP]
Affiliations
- PMID: 32690628
- DOI: 10.1126/scitranslmed.abc9396
Abstract
The COVID-19 pandemic, caused by infection with the SARS-CoV-2 coronavirus, is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale-up. Here, we developed an alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with Lipid InOrganic Nanoparticles (LION) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti-SARS-CoV-2 S protein IgG antibody isotypes indicative of a Type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in lung and spleen. Prime-only immunization of aged (17-month old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. Importantly, in nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in 5 intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.