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

Robert J. Hogan^3,

Lois A. Zitzow^3,

Mary M. Hitt^4,

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

Correspondence
B. Brett Finlay
bfinlay{at}interchange.ubc.ca

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 -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.

Present address: Departments of Anatomy and Radiology and Infectious Diseases, University of Georgia, Athens, GA 30602, USA.

Present address: Animal Resources Center, Department of Surgery, University of Chicago, Chicago, IL 60637, USA.

Present address: Cross Cancer Institute, Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.

||Present address: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

¶Present address: Tulane University School of Medicine, Department of Microbiology and Immunology, New Orleans, LA 70112, USA.

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