A recombinant selective drug-resistant M. bovis BCG enhances the bactericidal activity of a second-line anti-tuberculosis regimen - 18/09/21
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Abstract |
Drug-resistant tuberculosis (DR-TB) poses a new threat to global health; to improve the treatment outcome, therapeutic vaccines are considered the best chemotherapy adjuvants. Unfortunately, there is no therapeutic vaccine approved against DR-TB. Our study assessed the therapeutic efficacy of a recombinant drug-resistant BCG (RdrBCG) vaccine in DR-TB. We constructed the RdrBCG overexpressing Ag85B and Rv2628 by selecting drug-resistant BCG strains and transformed them with plasmid pEBCG or pIBCG to create RdrBCG-E and RdrBCG-I respectively. Following successful stability testing, we tested the vaccine’s safety in severe combined immune deficient (SCID) mice that lack both T and B lymphocytes plus immunoglobulins. Finally, we evaluated the RdrBCG’s therapeutic efficacy in BALB/c mice infected with rifampin-resistant M. tuberculosis and treated with a second-line anti-TB regimen. We obtained M. bovis strains which were resistant to several second-line drugs and M. tuberculosis resistant to rifampin. Notably, the exogenously inserted genes were lost in RdrBCG-E but remained stable in the RdrBCG-I both in vitro and in vivo. When administered adjunct to a second-line anti-TB regimen in a murine model of DR-TB, the RdrBCG-I lowered lung M. tuberculosis burden by 1 log10. Furthermore, vaccination with RdrBCG-I adjunct to chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG-I showed almost the same virulence as its parent BCG Tice strain in SCID mice. Our findings suggested that the RdrBCG-I was stable, safe and effective as a therapeutic vaccine. Hence, the “recombinant” plus “drug-resistant” BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | The RdrBCG-I overexpressing Ag85B + Rv2628 is stable both in vitro and in vivo. |
• | The RdrBCG-I was safe and nonvirulent even to SCID mice. |
• | The RdrBCG-I enhanced the activity of a second-line regimen in a murine model. |
• | The RdrBCG facilitated lung tissue recovery. |
Keywords : Drug-resistant tuberculosis, Therapeutic vaccine, Recombinant drug-resistant BCG, Ag85B, Rv2628
Plan
Vol 142
Article 112047- octobre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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