Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS
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Bukreyev, A
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Bukreyev, A
Lamirande, EW
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Lamirande, EW
Buchholz, UJ
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Buchholz, UJ
Vogel, LN
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Vogel, LN
Elkins, WR
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Elkins, WR
St Claire, M
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
St Claire, M
Murphy, BR
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Murphy, BR
Subbarao, K
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Subbarao, K
Collins, PL
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机构:NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
Collins, PL
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[1] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
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. Findings 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. Interpretation 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.