Immunogenicity and protection induced by a Mycobacterium tuberculosis sigE mutant in a BALB/c mouse model of progressive pulmonary tuberculosis.
Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine Mycobacterium bovis BCG. In this article, we analyze the potential use of an attenuated mutant of Mycobacterium tuberculosis H37Rv lacking the sigma factor sigma(E) as a live vaccine. We have demonstrated that BALB/c mice infected by the intratracheal route with this mutant strain showed significantly higher survival rates and less tissue damage than animals infected with the parental or complemented mutant strain. Although animals infected with the sigE mutant had low bacillary loads, their lungs showed significantly higher production of the protective factors gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), and beta-defensins than those of animals infected with the parental or complemented mutant strain. Moreover, we demonstrate that the sigE mutant, when inoculated subcutaneously, was more attenuated than BCG in immunodeficient nude mice, thus representing a good candidate for a novel attenuated live vaccine strain. Finally, when we used the sigE mutant as a subcutaneous vaccine, it was able to induce a higher level of protection than did BCG with both H37Rv and a highly virulent strain of M. tuberculosis (Beijing code 9501000). Taken together, our findings suggest that the sigE mutant is a very promising strain for the development of a new vaccine against tuberculosis.
Hernandez Pando
Rogelio
R
Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition Salvador Zubiràn, Mexico City, Mexico.
Aguilar
Leon Diana
LD
Smith
Issar
I
Manganelli
Riccardo
R
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D019001:Nitric Oxide Synthase / Q000032:analysis; D016133:Polymerase Chain Reaction; D012808:Sigma Factor / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D023083:beta-Defensins / Q000032:analysis
D001426:Bacterial Proteins; D012808:Sigma Factor; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; C111259:sigE protein, Bacteria; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase
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