Vaccination of mice with recombinant baculovirus expressing spike or nucleocapsid protein of SARS-like coronavirus generates humoral and cellular immune responses

Mol Immunol. 2008 Feb;45(4):868-75. doi: 10.1016/j.molimm.2007.08.010. Epub 2007 Oct 1.

Abstract

Continuous efforts have been made to develop a prophylactic vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, two recombinant baculoviruses, vAc-N and vAc-S, were constructed, which contained the mammalian-cell activate promoter element, human elongation factor 1alpha-subunit (EF-1alpha), the human cytomegalovirus (CMV) immediate-early promoter, and the nucleocapsid (N) or spike (S) gene of bat SARS-like CoV (SL-CoV) under the control of the CMV promoter. Mice were subcutaneously and intraperitoneally injected with recombinant baculovirus, and both humoral and cellular immune responses were induced in the vaccinated groups. The secretion level of IFN-gamma was much higher than that of IL-4 in vAc-N or vAc-S immunized groups, suggesting a strong Th1 bias towards cellular immune responses. Additionally, a marked increase of CD4 T cell immune responses and high levels of anti-SARS-CoV humoral responses were also detected in the vAc-N or vAc-S immunized groups. In contrast, there were significantly weaker cellular immune responses, as well as less antibody production than in the control groups. Our data demonstrates that the recombinant baculovirus can serve as an effective vaccine strategy. In addition, because effective SARS vaccines should act to not only prevent the reemergence of SARS-CoV, but also to provide cross-protection against SL-CoV, findings in this study may have implications for developing such cross-protective vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation*
  • Baculoviridae / genetics
  • Baculoviridae / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line
  • Coronavirus Nucleocapsid Proteins
  • Cricetinae
  • Immunity, Cellular*
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Nucleocapsid Proteins / biosynthesis*
  • Nucleocapsid Proteins / genetics
  • Promoter Regions, Genetic
  • Severe acute respiratory syndrome-related coronavirus / immunology*
  • Severe acute respiratory syndrome-related coronavirus / metabolism
  • Spike Glycoprotein, Coronavirus
  • Vaccination
  • Viral Envelope Proteins / biosynthesis*
  • Viral Envelope Proteins / genetics

Substances

  • Coronavirus Nucleocapsid Proteins
  • Membrane Glycoproteins
  • Nucleocapsid Proteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • Interleukin-4
  • Interferon-gamma