Development of a SARS-CoV-2 vaccine

National Institute Of Allergy And Infectious Diseases

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Abstract

We constructed a panel of recombinant MVAs that express unmodified or modified SARS-CoV-2 spike (S) protein. Intramuscular injection of mice with the rMVAs induced antibodies, which neutralized a pseudovirus in vitro and upon passive transfer protected hACE2 transgenic mice from lethal infection with SARS-CoV-2, as well as S-specific CD3+CD8+IFNg+ T cells. Antibody boosting occurred following a second rMVA or adjuvanted purified RBD protein. Immunity conferred by a single vaccination of transgenic hACE2 mice prevented morbidity and weight loss upon intranasal infection with SARS-CoV-2 three or seven weeks later. One or two rMVA vaccinations also prevented detection of infectious SARS-CoV-2 and subgenomic viral mRNAs in the lungs and greatly reduced induction of cytokine and chemokine mRNAs. A low amount of virus was found in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of low levels of subgenomic mRNAs in turbinates indicated that replication was aborted in immunized animals.