title: Protection by novel vaccine candidates, Mycobacterium tuberculosis ΔmosR and ΔechA7, against challenge with a Mycobacterium tuberculosis Beijing strain.
abstract: Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), infects over two billion people, claiming around 1.5 million lives annually. The only vaccine approved for clinical use against this disease is the Bacillus Calmette-Guérin (BCG) vaccine. Unfortunately, BCG has limited efficacy against the adult, pulmonary form of tuberculosis. This vaccine was developed from M. bovis with antigen expression and host specificity that differ from M. tuberculosis. To address these problems, we have designed two novel, live attenuated vaccine (LAV) candidates on an M. tuberculosis background: ΔmosR and ΔechA7. These targeted genes are important to M. tuberculosis pathogenicity during infection. To examine the efficacy of these strains, C57BL/6 mice were vaccinated subcutaneously with either LAV, BCG, or PBS. Both LAV strains persisted up to 16 weeks in the spleens or lungs of vaccinated mice, while eliciting minimal pathology prior to challenge. Following challenge with a selected, high virulence M. tuberculosis Beijing strain, protection was notably greater for both groups of LAV vaccinated animals as compared to BCG at both 30 and 60 days post-challenge. Additionally, vaccination with either ΔmosR or ΔechA7 elicited an immune response similar to BCG. Although these strains require further development to meet safety standards, this first evidence of protection by these two new, live attenuated vaccine candidates shows promise.
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: samarcus@wisc.edu.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Marcus
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: steinbeh@vetmed.wisc.edu.
authors.forename: Howard
authors.initials: H
authors.lastname: Steinberg
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. Electronic address: atalaat@wisc.edu.
authors.forename: Adel M
authors.initials: AM
authors.lastname: Talaat
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D058491:Bacterial Load; D016207:Cytokines / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated
keywords: BCG; Beijing strain; Live attenuated vaccine; Mycobacterium tuberculosis; Tuberculosis