Journal article
Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease
Virology, Vol.399(1), pp.120-128
03/30/2010
DOI: 10.1016/j.virol.2010.01.004
PMCID: PMC2830353
PMID: 20110095
Abstract
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-ΔE or SARS-CoV-Δ[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 from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-ΔE and rSARS-CoV-Δ[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-ΔE is an efficacious vaccine candidate that might be useful if SARS recurred.
Details
- Title: Subtitle
- Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease
- Creators
- Jason Netland - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242Marta L DeDiego - Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, SpainJincun Zhao - Department of Microbiology, University of Iowa, Iowa City, IA 52242Craig Fett - Department of Microbiology, University of Iowa, Iowa City, IA 52242Enrique Álvarez - Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, SpainJosé L Nieto-Torres - Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, SpainLuis Enjuanes - Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, SpainStanley Perlman - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Virology, Vol.399(1), pp.120-128
- DOI
- 10.1016/j.virol.2010.01.004
- PMID
- 20110095
- PMCID
- PMC2830353
- NLM abbreviation
- Virology
- ISSN
- 0042-6822
- eISSN
- 1096-0341
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: PO1 AI060699-01, RO1 AI079424-01A1, T32 AI007533; DOI: 10.13039/501100000780, name: European Commission, award: 223498; DOI: 10.13039/501100003176, name: Ministerio de Educación, Cultura y Deporte, award: BIO2007-60978
- Language
- English
- Date published
- 03/30/2010
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777472602771
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