期刊
VIROLOGY
卷 399, 期 1, 页码 120-128出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.01.004
关键词
Severe acute respiratory syndrome; Rodent model; Vaccine; Coronavirus; Respiratory virus; T cell response
类别
资金
- National Institutes of Health (US) [PO1 AI060699-01, RO1 AI079424-01A1]
- Ministry of Education and Science of Spain [BIO2007-60978]
- European Commission [223498]
- NIH [T32 AI007533]
The severe acute respiratory syndrome coronavirus (SARS-CoV) caused substantial morbidity and Mortality in 2002-2003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-Delta E or SARS-CoV-Delta[E,6-9b] (deleted in accessory proteins (6, 7a, 7b, 8a, 8b, 9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and Partly protected hACE2 Tg mice front lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-Delta E and rSARS-CoV-Delta[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-Delta E is an efficacious vaccine candidate that might be useful if SARS recurred. (C) 2010 Elsevier Inc. All rights reserved.
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