title: Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.
abstract: 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.
authors.affiliation: University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: See
authors.affiliation: University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Petric
authors.affiliation: University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lawrence
authors.affiliation: University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
authors.forename: Catherine P Y
authors.initials: CPY
authors.lastname: Mok
authors.affiliation: Southern Research Institute, Birmingham, AL 35205, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rowe
authors.affiliation: Southern Research Institute, Birmingham, AL 35205, USA.
authors.forename: Lois A
authors.initials: LA
authors.lastname: Zitzow
authors.affiliation: University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
authors.forename: Karuna P
authors.initials: KP
authors.lastname: Karunakaran
authors.affiliation: Southern Research Institute, Birmingham, AL 35205, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Voss
authors.affiliation: University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
authors.affiliation: Departments of Pathology and Molecular Medicine and Biology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.affiliation: Michael Smith Laboratories and Departments of Biochemistry and Molecular Biology and Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.affiliation: Brody School of Medicine, Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Roper