Protection by novel vaccine candidates, Mycobacterium tuberculosis ΔmosR and ΔechA7, against challenge with a Mycobacterium tuberculosis Beijing strain. Issue 42 (13th October 2015)

• Record Type: Journal Article
• Authors: Marcus, Sarah A.; Steinberg, Howard; Talaat, Adel M.
• Is Part Of: Vaccine. Volume 33:Issue 42(2015)
• Page Start: 5633
• Page End: 5639
• Publication Date: 2015-10-13
• Subjects: Mycobacterium tuberculosis -- Live attenuated vaccine -- Tuberculosis -- BCG -- Beijing strain; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.08.084
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: The currently used BCG vaccine does not protect against pulmonary TB. Genes induced during mouse infection were targeted yielding LAVs Δ mosR and Δ echA7 . Both LAV strains provide protection against an M. tuberculosis Beijing strain challenge. Both provided improved protection over BCG in terms of bacterial load and pathology. Both gave an M. tuberculosis specific immune response and persisted within the host. 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: Δ mosR and Δ echA7 . 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 Δ mosR or Δ echA7 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.