title: Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS.
abstract: BACKGROUND
  The outbreak of severe acute respiratory syndrome (SARS) in 2002 was caused by a previously unknown coronavirus-SARS coronavirus (SARS-CoV). We have developed an experimental SARS vaccine for direct immunisation of the respiratory tract, the major site of SARS- coronavirus transmission and disease.
  
  
  METHODS
  We expressed the complete SARS coronavirus envelope spike (S) protein from a recombinant attenuated parainfluenza virus (BHPIV3) that is being developed as a live attenuated, intranasal paediatric vaccine against human parainfluenza virus type 3 (HPIV3). We immunised eight African green monkeys, four with a single dose of BHPIV3/ SARS-S and four with a control, BHPIV3/Ctrl, administered via the respiratory tract. A SARS-coronavirus challenge was given to all monkeys 28 days after immunisation.
  
  
  RESULTS
  Immunisation of animals with BHPIV3/SARS-S induced the production of SARS-coronavirus-neutralising serum antibodies, indicating that a systemic immune response resulted from mucosal immunisation. After challenge with SARS coronavirus, all monkeys in the control group shed SARS coronavirus, with shedding lasting 5-8 days. No viral shedding occurred in the group immunised with BHPIV3/SARS-S.
  
  
  CONCLUSIONS
  A vectored mucosal vaccine expressing the SARS-coronavirus S protein alone may be highly effective in a single-dose format for the prevention of SARS.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. AB176v@nih.gov
authors.forename: Alexander
authors.initials: A
authors.lastname: Bukreyev
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Lamirande
authors.forename: Ursula J
authors.initials: UJ
authors.lastname: Buchholz
authors.forename: Leatrice N
authors.initials: LN
authors.lastname: Vogel
authors.forename: William R
authors.initials: WR
authors.lastname: Elkins
authors.forename: Marisa
authors.initials: M
authors.lastname: St Claire
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D004274:DNA, Recombinant; D018928:Immunity, Mucosal; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D009297:Nasal Mucosa / Q000821:virology; D022241:Parainfluenza Vaccines; D029101:Parainfluenza Virus 3, Bovine / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D007507:Therapeutic Irrigation; D014132:Trachea; D014611:Vaccination; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004274:DNA, Recombinant; D008562:Membrane Glycoproteins; D022241:Parainfluenza Vaccines; D064370:Spike Glycoprotein, Coronavirus; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus