Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease.
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-DeltaE 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 from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-DeltaE 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-DeltaE is an efficacious vaccine candidate that might be useful if SARS recurred.
Netland
Jason
J
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242.
DeDiego
Marta L
ML
Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Zhao
Jincun
J
Department of Microbiology, University of Iowa, Iowa City, IA 52242.
Fett
Craig
C
Department of Microbiology, University of Iowa, Iowa City, IA 52242.
Álvarez
Enrique
E
Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Nieto-Torres
José L
JL
Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Enjuanes
Luis
L
Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Perlman
Stanley
S
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City, IA 52242. Electronic address: Stanley-Perlman@uiowa.edu.
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014613:Vaccines, Attenuated / Q000627:therapeutic use*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000502:physiology*; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; C501689:E protein, SARS coronavirus; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D000086082:Viroporin Proteins