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.
See
Raymond H
RH
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Zakhartchouk
Alexander N
AN
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Petric
Martin
M
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Lawrence
David J
DJ
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Mok
Catherine P Y
CPY
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Hogan
Robert J
RJ
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Rowe
Thomas
T
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Zitzow
Lois A
LA
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Karunakaran
Karuna P
KP
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Hitt
Mary M
MM
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Graham
Frank L
FL
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Prevec
Ludvik
L
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Mahony
James B
JB
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Sharon
Chetna
C
Departments of Molecular and Medical Genetics and Microbiology and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Auperin
Thierry C
TC
Departments of Molecular and Medical Genetics and Microbiology and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Rini
James M
JM
Departments of Molecular and Medical Genetics and Microbiology and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Tingle
Aubrey J
AJ
Michael Smith Foundation for Health Research, Vancouver, BC V6H 3X8, Canada.
Scheifele
David W
DW
Vaccine Evaluation Centre, British Columbia Institute for Children's and Women's Health, BC Children's Hospital, Vancouver, BC V6H 3V4, Canada.
Skowronski
Danuta M
DM
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Patrick
David M
DM
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Voss
Thomas G
TG
Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205, USA.
Babiuk
Lorne A
LA
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Gauldie
Jack
J
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Roper
Rachel L
RL
Brody School of Medicine, Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA.
Brunham
Robert C
RC
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Finlay
B Brett
BB
Michael Smith Laboratories and Departments of Biochemistry and Molecular Biology and Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
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