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

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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 β-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.

authors

  • See, Raymond H
  • Zakhartchouk, Alexander N
  • Petric, Martin
  • Lawrence, David J
  • Mok, Catherine PY
  • Hogan, Robert J
  • Rowe, Thomas
  • Zitzow, Lois A
  • Karunakaran, Karuna P
  • Hitt, Mary M
  • Graham, Frank Lawson
  • Prevec, Ludvik
  • Mahony, James Benson
  • Sharon, Chetna
  • Auperin, Thierry C
  • Rini, James M
  • Tingle, Aubrey J
  • Scheifele, David W
  • Skowronski, Danuta M
  • Patrick, David M
  • Voss, Thomas G
  • Babiuk, Lorne A
  • Gauldie, Jack
  • Roper, Rachel L
  • Brunham, Robert C
  • Finlay, B Brett

publication date

  • March 1, 2006

has subject area