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

Author:

See Raymond H.1,Zakhartchouk Alexander N.2,Petric Martin1,Lawrence David J.1,Mok Catherine P. Y.1,Hogan Robert J.3,Rowe Thomas3,Zitzow Lois A.3,Karunakaran Karuna P.1,Hitt Mary M.4,Graham Frank L.4,Prevec Ludvik4,Mahony James B.4,Sharon Chetna5,Auperin Thierry C.5,Rini James M.5,Tingle Aubrey J.6,Scheifele David W.7,Skowronski Danuta M.1,Patrick David M.1,Voss Thomas G.3,Babiuk Lorne A.2,Gauldie Jack4,Roper Rachel L.8,Brunham Robert C.1,Finlay B. Brett9

Affiliation:

1. University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada

2. Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada

3. Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA

4. Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada

5. Departments of Molecular and Medical Genetics and Microbiology and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada

6. Michael Smith Foundation for Health Research, Vancouver, BC V6H 3X8, Canada

7. Vaccine Evaluation Centre, British Columbia Institute for Children's and Women's Health, BC Children's Hospital, Vancouver, BC V6H 3V4, Canada

8. Brody School of Medicine, Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA

9. Michael Smith Laboratories and Departments of Biochemistry and Molecular Biology and Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada

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 byβ-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.

Publisher

Microbiology Society

Subject

Virology

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