Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus

J Gen Virol. 2006 Mar;87(Pt 3):641-50. doi: 10.1099/vir.0.81579-0.

Abstract

Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • Antibody Specificity
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Female
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Neutralization Tests
  • Nucleocapsid Proteins / genetics
  • SARS Virus / chemistry
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Spike Glycoprotein, Coronavirus
  • Vaccination*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / administration & dosage*

Substances

  • Antibodies, Viral
  • Immunoglobulin A
  • MHV surface projection glycoprotein
  • Membrane Glycoproteins
  • Nucleocapsid Proteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, DNA
  • Viral Envelope Proteins
  • Viral Vaccines
  • spike glycoprotein, SARS-CoV