Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS.
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.
Bukreyev
Alexander
A
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. AB176v@nih.gov
Lamirande
Elaine W
EW
Buchholz
Ursula J
UJ
Vogel
Leatrice N
LN
Elkins
William R
WR
St Claire
Marisa
M
Murphy
Brian R
BR
Subbarao
Kanta
K
Collins
Peter L
PL
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*
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