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Novel Bacterial Delivery System with Attenuated Salmonella typhimurium Carrying Plasmid Encoding Mtb Antigen 85A for Mucosal Immunization: Establishment of Proof of Principle in TB Mouse Model
Author(s) -
PARIDA SHREEMANTA K.,
HUYGEN KRIS,
RYFFEL BERNHARD,
CHAKRABORTY TRINAD
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1352.030
Subject(s) - vaccination , tuberculosis vaccines , immunization , dna vaccination , salmonella , virology , mycobacterium tuberculosis , antigen , immune system , aroa , tuberculosis , biology , plasmid , attenuated vaccine , naked dna , mycobacterium bovis , microbiology and biotechnology , immunology , virulence , medicine , gene , bacteria , enterobacteriaceae , escherichia coli , genetics , pathology
Tuberculosis (TB), the leading killer of young adults worldwide, newly affects one person every second and kills one in every 15 seconds. The recent increase of TB in developing countries has been exacerbated by many causes including pandemic HIV, war and political instability, drug resistance, and increasing poverty. Genetic immunization has emerged with tremendous potential in vaccination against TB with success in animal models with naked DNA encoding different genes such as Ag85A, Pst3, and hsp65. However, there are shortcomings in translating this success into reality in human clinical trials due to limitations at the level of delivery, quality, and quantity of DNA to be administered, which can be circumvented by using an attenuated bacteria delivery system for transgene vaccination for mucosal immunization targeting the inductive sites of the immune system. We compare this novel delivery system using an attenuated Salmonella Δ aroA strain through a mucosal route with classic intramuscular DNA delivery using a potential protective antigen, Ag85A, of Mycobacterium tuberculosis in a mouse infection virulent challenge model. We show an immune response and superior protection in the mice at the level of the lungs as well as the spleen against a virulent challenge after intranasal immunization by recombinant Salmonella typhimurium carrying a eukaryotic expression plasmid encoding Ag85A rather than the classic DNA immunization and at par with the protection conferred by BCG. This study establishes the proof of principle of this system for further exploitation of this platform for vaccine development, which is being pursued for postexposure vaccine development for TB.