Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus

Abstract

Two 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 infection