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Comparative Study
. 2006 Mar;87(Pt 3):641-650.
doi: 10.1099/vir.0.81579-0.

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

Raymond H See  1 , Alexander N Zakhartchouk  2 , Martin Petric  1 , David J Lawrence  1 , Catherine P Y Mok  1 , Robert J Hogan  3 , Thomas Rowe  3 , Lois A Zitzow  3 , Karuna P Karunakaran  1 , Mary M Hitt  4 , Frank L Graham  4 , Ludvik Prevec  4 , James B Mahony  4 , Chetna Sharon  5 , Thierry C Auperin  5 , James M Rini  5 , Aubrey J Tingle  6 , David W Scheifele  7 , Danuta M Skowronski  1 , David M Patrick  1 , Thomas G Voss  3 , Lorne A Babiuk  2 , Jack Gauldie  4 , Rachel L Roper  8 , Robert C Brunham  1 , B Brett Finlay  9
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Comparative Study

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

Raymond H See et al. J Gen Virol. 2006 Mar.

Abstract

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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