An Alphavirus -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates
Open Access
- 5 August 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 12 (555)
- https://doi.org/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.Keywords
Funding Information
- National Institute of General Medical Sciences (R01GM120553)
- National Institute of Allergy and Infectious Diseases (P51OD010425)
- National Institute of Allergy and Infectious Diseases (27220140006C)
- National Institute of Allergy and Infectious Diseases (75N93019C00037)
- National Institute of Allergy and Infectious Diseases (HHSN272201700059C)
- National Institute of Allergy and Infectious Diseases (1F32AI136371)
- Burroughs Wellcome Fund (Investigators in the pathogenesis of infectious disease award)
- Pew Charitable Trusts (Pew Biomedical Scholars Award)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- University of Washington Center for Innate Immunity and Immune Disease
- Washington Research Foundation (WRF Postdoctoral Fellowship)
This publication has 76 references indexed in Scilit:
- Thyroid Cancer Risk Is Not Increased in Diabetic PatientsPLOS ONE, 2012
- Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS VirusPLOS ONE, 2012
- Sensing of RNA Viruses: a Review of Innate Immune Receptors Involved in Recognizing RNA Virus InvasionJournal of Virology, 2012
- T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected MiceJournal of Virology, 2010
- The spike protein of SARS-CoV — a target for vaccine and therapeutic developmentNature Reviews Microbiology, 2009
- Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus ChallengeJournal of Virology, 2008
- Development and preclinical evaluation of an alphavirus replicon vaccine for influenzaVaccine, 2007
- Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirusVaccine, 2007
- SARS Vaccine DevelopmentEmerging Infectious Diseases, 2005
- An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirusNature Medicine, 2004