An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), 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 (LIONs) 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 the lung and spleen. Prime-only immunization of aged (17 months old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. In nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in five 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.
Department of Microbiology, University of Washington, Seattle, WA 98109, USA. HDT Bio, Seattle, WA 98102, USA.HDT Bio, Seattle, WA 98102, USA. PAI Life Sciences, Seattle, WA 98102, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA. Washington National Primate Research Center, Seattle, WA 98121, USA.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA. Department of Immunology, University of Washington, Seattle, WA 98109, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA. PAI Life Sciences, Seattle, WA 98102, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA. Washington National Primate Research Center, Seattle, WA 98121, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA.Washington National Primate Research Center, Seattle, WA 98121, USA.HDT Bio, Seattle, WA 98102, USA.HDT Bio, Seattle, WA 98102, USA. PAI Life Sciences, Seattle, WA 98102, USA. Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA.HDT Bio, Seattle, WA 98102, USA. Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.Washington National Primate Research Center, Seattle, WA 98121, USA. Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA. Department of Immunology, University of Washington, Seattle, WA 98109, USA.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.HDT Bio, Seattle, WA 98102, USA.Department of Microbiology, University of Washington, Seattle, WA 98109, USA. fullerdh@uw.edu. Washington National Primate Research Center, Seattle, WA 98121, USA. Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA. MeSH
AlphavirusAnimalsAntibodies, NeutralizingAntibody FormationBetacoronavirusCOVID-19COVID-19 VaccinesCoronavirus InfectionsInorganic ChemicalsLipidsMiceMice, Inbred BALB CMice, Inbred C57BLNanoparticlesPandemicsPneumonia, ViralPrimatesRNA, ViralRepliconSARS-CoV-2T-LymphocytesViral Vaccines
Pub Type(s)
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
