COMPARATIVE STUDY
JOURNAL ARTICLE

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

Raymond H See, Alexander N Zakhartchouk, Martin Petric, David J Lawrence, Catherine P Y Mok, Robert J Hogan, Thomas Rowe, Lois A Zitzow, Karuna P Karunakaran, Mary M Hitt, Frank L Graham, Ludvik Prevec, James B Mahony, Chetna Sharon, Thierry C Auperin, James M Rini, Aubrey J Tingle, David W Scheifele, Danuta M Skowronski, David M Patrick, Thomas G Voss, Lorne A Babiuk, Jack Gauldie, Rachel L Roper, Robert C Brunham, B Brett Finlay
Journal of General Virology 2006, 87: 641-50
16476986
Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-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 neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.

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