Protection against plague afforded by immunisation with DNA vaccines optimised for expression of the Yersinia pestis V antigen.
DNA vaccine vectors were produced which were optimised for expression of the Yersinia pestis V antigen in the BALB/c mouse model. Six different eukaryotic promoters were compared, resulting in the selection of the CMV promoter with an additional translational enhancer downstream. Surprisingly, alteration of the codon usage of the lcrV gene encoding V antigen for expression in murine cells was not found to improve the antibody responses generated against V antigen. The DNA vaccine was subsequently evaluated in its delivery via intramuscular injection compared to gene-gun administration. Gene-gun delivery was found to induce significantly higher V antigen-specific antibody responses and also afforded the highest level of protection against Y. pestis challenge. In addition, the protection achieved could be increased by using a 'prime and boost' strategy, administering the DNA vaccine followed by recombinant V antigen. These results show promise for a DNA vaccine against plague.
Garmory
Helen S
HS
Dstl Chemical and Biological Sciences, Porton Down, Salisbury SP4 0JQ, UK. hsgarmory@dstl.gov.uk
Freeman
Donna
D
Brown
Katherine A
KA
Titball
Richard W
RW
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D019470:Biolistics; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000276:immunology* / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology*
D000942:Antigens, Bacterial; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA