Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus.
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.
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Raymond H
RH
See
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Alexander N
AN
Zakhartchouk
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Martin
M
Petric
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
David J
DJ
Lawrence
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Catherine P Y
CPY
Mok
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Robert J
RJ
Hogan
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Thomas
T
Rowe
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Lois A
LA
Zitzow
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Karuna P
KP
Karunakaran
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Mary M
MM
Hitt
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Frank L
FL
Graham
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Ludvik
L
Prevec
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
James B
JB
Mahony
Departments of Molecular and Medical Genetics and Microbiology and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Chetna
C
Sharon
Departments of Molecular and Medical Genetics and Microbiology and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Thierry C
TC
Auperin
Departments of Molecular and Medical Genetics and Microbiology and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
James M
JM
Rini
Michael Smith Foundation for Health Research, Vancouver, BC V6H 3X8, Canada.
Aubrey J
AJ
Tingle
Vaccine Evaluation Centre, British Columbia Institute for Children's and Women's Health, BC Children's Hospital, Vancouver, BC V6H 3V4, Canada.
David W
DW
Scheifele
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Danuta M
DM
Skowronski
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
David M
DM
Patrick
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Thomas G
TG
Voss
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Lorne A
LA
Babiuk
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Jack
J
Gauldie
Brody School of Medicine, Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA.
Rachel L
RL
Roper
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Robert C
RC
Brunham
Michael Smith Laboratories and Departments of Biochemistry and Molecular Biology and Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
B Brett
BB
Finlay
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000918:Antibody Specificity; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins / Q000235:genetics; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; D019590:Nucleocapsid Proteins; D064370:Spike Glycoprotein, Coronavirus; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus