A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice

Nature. 2004 Apr 1;428(6982):561-4. doi: 10.1038/nature02463.

Abstract

Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • SARS Virus / genetics
  • SARS Virus / immunology*
  • SARS Virus / physiology
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Vaccination
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Virus Replication

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Glycoproteins
  • Vaccines, DNA
  • Viral Vaccines