Mucosal Immunisation of African Green Monkeys (Cercopithecus Aethiops) With an Attenuated Parainfluenza Virus Expressing the SARS Coronavirus Spike Protein for the Prevention of SARS

Lancet. 2004 Jun 26;363(9427):2122-7. doi: 10.1016/S0140-6736(04)16501-X.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood
  • Chlorocebus aethiops
  • DNA, Recombinant
  • Immunity, Mucosal
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Nasal Mucosa / virology
  • Parainfluenza Vaccines
  • Parainfluenza Virus 3, Bovine / immunology*
  • Parainfluenza Virus 3, Bovine / isolation & purification
  • Parainfluenza Virus 3, Bovine / metabolism
  • Respiratory Mucosa / immunology*
  • SARS Virus / immunology*
  • SARS Virus / isolation & purification
  • SARS Virus / metabolism
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Spike Glycoprotein, Coronavirus
  • Therapeutic Irrigation
  • Trachea
  • Vaccination*
  • Vaccines, Attenuated
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • DNA, Recombinant
  • MHV surface projection glycoprotein
  • Membrane Glycoproteins
  • Parainfluenza Vaccines
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Attenuated
  • Viral Envelope Proteins
  • Viral Vaccines
  • spike glycoprotein, SARS-CoV