Optimization of a DNA vaccine against SARS.
Severe acute respiratory syndrome coronavirus (SARS-CoV) first appeared in Southern China in November 2002, and then quickly spread to 33 countries on five continents along international air travel routes. Although the SARS epidemic has been contained, there is a clear need for a safe and effective vaccine should an outbreak of a SARS-CoV infection reappear in human population. In this study, we tested four DNA-vaccine constructs: (1) pLL70, containing cDNA for the SARS-CoV spike (S) gene; (2) pcDNA-SS, containing codon-optimized S gene for SARS-CoV S protein (residues 12-1255) fused with a leader sequence derived from the human CD5 gene; (3) pcDNA-St, containing the gene encoding the N-portion of the codon-optimized S gene (residues 12-532) with the CD5 leader sequence; (4) pcDNA-St-VP22C, containing the gene encoding the N-portion of the codon-optimized S protein with the CD5 leader sequence fused with the C-terminal 138 amino acids of the bovine herpesvirus-1 (BHV-1) major tegument protein VP22. Each of these plasmids was intradermally administered to C57BL/6 mice in three separate immunizations. Analysis of humoral and cellular immune responses in immunized mice demonstrated that pcDNA-SS and pcDNA-St-VP22C are the most immunogenic SARS vaccine candidates.
Zakhartchouk
Alexander N
AN
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada. alex.zak@usask.ca
Viswanathan
Sathiyanarayanan
S
Moshynskyy
Igor
I
Petric
Martin
M
Babiuk
Lorne A
LA
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D018956:CD5 Antigens / Q000235:genetics; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010957:Plasmids; D021382:Protein Sorting Signals; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control; D064370:Spike Glycoprotein, Coronavirus; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D018956:CD5 Antigens; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D064370:Spike Glycoprotein, Coronavirus; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; C434023:tegument protein VP22, bovine herpesvirus 1