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

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, S