Protection against Leishmania donovani infection by DNA vaccination: increased DNA vaccination efficiency through inhibiting the cellular p53 response.
DNA-vaccination holds great promise for the future of vaccine development against infectious diseases, especially in developing countries. We therefore investigated the possibility of using DNA-vaccination against Leishmania donovani infection with the A2 virulence gene and whether inhibiting the cellular p53 response could increase the effectiveness of the A2 DNA vaccine. p53, also known as the guardian of the genome, is activated following DNA transfection and has pleotropic effects on cells, which could have adverse effects on the effectiveness of DNA-vaccination. Two major observations are reported within. First, vaccination with the A2 gene induced both humoral and cellular immune responses against A2 which provided significant protection against infection with L. donovani. Second, inhibition of p53 with human papillomavirus E6 resulted in higher expression of heterologous transfected genes in vitro and more efficient DNA-vaccination in vivo. These results have important implications for DNA vaccination against leishmaniasis and potentially against other infectious diseases.
Ghosh
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A
Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, H3A 2B4, Quebec, Canada.
Labrecque
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Matlashewski
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G
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D017125:Genes, Protozoan; D016158:Genes, p53; D006801:Humans; D007893:Leishmania donovani / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000494:pharmacology*; D014774:Virulence / Q000235:genetics
D000913:Antibodies, Protozoan; D017931:DNA Primers; D016052:Protozoan Vaccines; D019444:Vaccines, DNA