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 ce...

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Bibliographic Details
Published in:Vaccine 2001-04, Vol.19 (23-24), p.3169-3178
Main Authors: Ghosh, Anirban, Labrecque, Sylvie, Matlashewski, Greg
Format: Article
Language:English
Subjects:
AA2 gene
Animals
Antibodies, Protozoan - biosynthesis
Base Sequence
Biological and medical sciences
Cell Line
DNA Primers - genetics
DNA vaccine
Female
Fundamental and applied biological sciences. Psychology
Gene Deletion
Genes, p53
Genes, Protozoan
HPV E6
Humans
Leishmania
Leishmania donovani
Leishmania donovani - genetics
Leishmania donovani - immunology
Leishmania donovani - pathogenicity
Leishmaniasis, Visceral - genetics
Leishmaniasis, Visceral - immunology
Leishmaniasis, Visceral - prevention & control
Mice
Mice, Inbred BALB C
p53
p53 protein
Protozoa
Protozoan Vaccines - pharmacology
T-Lymphocytes, Helper-Inducer - immunology
Transfection
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, DNA - pharmacology
Virulence - genetics
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Summary: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.
ISSN:0264-410X
1873-2518
DOI:10.1016/S0264-410X(01)00023-8