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

• Published in: Nature Vol. 428; no. 6982; pp. 561 - 564
• Main Authors: Nabel, Gary J, Yang, Zhi-yong, Kong, Wing-pui, Huang, Yue, Roberts, Anjeanette, Murphy, Brian R, Subbarao, Kanta
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.04.2004; Nature Publishing Group; Nature Publishing Group UK
• Subjects: Adoptive Transfer; Animal models; Animals; Antibodies, Viral - immunology; Antigens, Viral - genetics; Antigens, Viral - immunology; AS protein; Biological and medical sciences; Deoxyribonucleic acid; DNA; DNA vaccines; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Glycoproteins - genetics; Glycoproteins - immunology; Immune system; Immunization; Lung - virology; Medical research; Mice; Mice, Inbred BALB C; Microbiology; Neutralization; Neutralization Tests; Prevention; Public health; S protein; SARS coronavirus; SARS Virus - genetics; SARS Virus - immunology; SARS Virus - physiology; Severe acute respiratory syndrome; Severe Acute Respiratory Syndrome - immunology; Severe Acute Respiratory Syndrome - prevention & control; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Testing; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Viral Vaccines - genetics; Viral Vaccines - immunology; Virology; Virus Replication; United States; Immunoprotection; Animal model; Rodentia; Glycoprotein; Genetic vaccine; Virus; Vertebrata; Mammalia; Coronavirus; Mouse; Coronaviridae; Nidovirales; Humoral immunity
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02463

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.