Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS

Alexander Bukreyev, Elaine W. Lamirande, Ursula J. Buchholz, Leatrice N. Vogel, William R. Elkins, Marisa St Claire, Brian R. Murphy, Kanta Subbarao, Peter L. Collins

Research output: Contribution to journalArticle

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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. 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.

Original languageEnglish (US)
Pages (from-to)2122-2127
Number of pages6
JournalLancet
Volume363
Issue number9427
DOIs
StatePublished - Jun 26 2004
Externally publishedYes

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Coronavirus Spike Glycoproteins
SARS Virus
Paramyxoviridae Infections
Cercopithecus aethiops
Severe Acute Respiratory Syndrome
Immunization
Coronavirus
Human parainfluenza virus 3
Vaccines
Respiratory System
Haplorhini
Virus Shedding
Mucosal Immunity
Protein S

ASJC Scopus subject areas

  • Medicine(all)

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Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. / Bukreyev, Alexander; Lamirande, Elaine W.; Buchholz, Ursula J.; Vogel, Leatrice N.; Elkins, William R.; St Claire, Marisa; Murphy, Brian R.; Subbarao, Kanta; Collins, Peter L.

In: Lancet, Vol. 363, No. 9427, 26.06.2004, p. 2122-2127.

Research output: Contribution to journalArticle

Bukreyev, Alexander ; Lamirande, Elaine W. ; Buchholz, Ursula J. ; Vogel, Leatrice N. ; Elkins, William R. ; St Claire, Marisa ; Murphy, Brian R. ; Subbarao, Kanta ; Collins, Peter L. / Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. In: Lancet. 2004 ; Vol. 363, No. 9427. pp. 2122-2127.
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