Roper, Rachel L.2021-04-122021-04-122006-03-01http://hdl.handle.net/10342/8915Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for theirability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection.A whole killed (inactivated byb-propiolactone) SARS-CoV vaccine and a combination of twoadenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike(S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizingantibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoVreplication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv micewas more effective than the Ad S/N vaccine administered either intranasally or intramuscularlyin inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of theWKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not withcellular immune responses as measured by gamma interferon secretion by mouse splenocytes.Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasallyor intramuscularly were significantly lower than those induced by the WKV vaccine. However,Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoVreplication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in thesera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play arole in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated micecontained antibodies to S, further suggesting a role for this protein in conferring protective immunityagainst SARS-CoV infectionen-USArticlehttps://doi.org/10.1099/vir.0.81579-0