Inactivated SARS-CoV Vaccine Elicits High Titers of Spike Protein-Specific Antibodies That Block Receptor Binding and Virus Entry

Biochem Biophys Res Commun. 2004 Dec 10;325(2):445-52. doi: 10.1016/j.bbrc.2004.10.052.

Abstract

The only severe acute respiratory syndrome (SARS) vaccine currently being tested in clinical trial consists of inactivated severe acute respiratory syndrome-associate coronavirus (SARS-CoV). However, limited information is available about host immune responses induced by the inactivated SARS vaccine. In this study, we demonstrated that SARS-CoV inactivated by beta-propiolactone elicited high titers of antibodies in the immunized mice and rabbits that recognize the spike (S) protein, especially the receptor-binding domain (RBD) in the S1 region. The antisera from the immunized animals efficiently bound to the RBD and blocked binding of RBD to angiotensin-converting enzyme 2, the functional receptor on the susceptible cells for SARS-CoV. With a sensitive and quantitative single-cycle infection assay using pseudovirus bearing the SARS-CoV S protein, we demonstrated that mouse and rabbit antisera significantly inhibited S protein-mediated virus entry with mean 50% inhibitory titers of 1:7393 and 1:2060, respectively. These data suggest that the RBD of S protein is a major neutralization determinant in the inactivated SARS vaccine which can induce potent neutralizing antibodies to block SARS-CoV entry. However, caution should be taken in using the inactivated SARS-CoV as a vaccine since it may also cause harmful immune and/or inflammatory responses.

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology*
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacology
  • Carboxypeptidases / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Immune Sera / immunology
  • Mice
  • Mice, Inbred BALB C
  • Peptidyl-Dipeptidase A
  • Protein Binding
  • Protein Structure, Tertiary
  • Rabbits
  • Receptors, Virus / immunology
  • Receptors, Virus / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • SARS Virus / immunology*
  • Vaccines, Inactivated / immunology
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Vaccines / immunology*
  • Viral Vaccines / pharmacology

Substances

  • Antibodies, Viral
  • Antiviral Agents
  • Immune Sera
  • Receptors, Virus
  • Recombinant Proteins
  • Vaccines, Inactivated
  • Viral Envelope Proteins
  • Viral Vaccines
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2