Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.
Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.
See
Raymond H
RH
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, 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.
Rowe
Thomas
T
Southern Research Institute, Birmingham, AL 35205, USA.
Zitzow
Lois A
LA
Southern Research Institute, Birmingham, AL 35205, USA.
Karunakaran
Karuna P
KP
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Voss
Thomas G
TG
Southern Research Institute, Birmingham, AL 35205, USA.
Brunham
Robert C
RC
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Gauldie
Jack
J
Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, 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, Canada.
Roper
Rachel L
RL
Brody School of Medicine, Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA.