ПРОФИЛАКТИКА ТУБЕРКУЛЕЗА: СОВРЕМЕННЫЕ ПОДХОДЫ К РАЗРАБОТКЕ ПРОТИВОТУБЕРКУЛЕЗНЫХ ВАКЦИН

This review is focused on recent advances in development of new vaccines for the prevention of tuberculosis. The main reasons for lack of BCG vaccine efficacy in different populations and geographic regions are presented. Design of new vaccines based on live modified strains of Mycobacterium bovis BCG, attenuated strains of Mycobacterium tuberculosis, recombinant proteins and viral vectors is considered in the specific examples. The usage of the heterologous «prime-boost» vaccination strategy against tuberculosis is discussed. В обзоре освещены современные достижения в области разработки новых вакцин для профилактики туберкулеза. Представлены основные причины недостаточной эффективности вакцины БЦЖ в различных популяциях и географических регионах. На конкретных примерах рассмотрены направления дизайна новых вакцин на основе живых модифицированных штаммов Mycobacterium bovis БЦЖ, аттенуированных штаммов Mycobacterium tuberculosis, рекомбинантных белков и вирусных векторов. Обсуждается перспектива применения схемы гетерологичной «prime-boost» вакцинации против туберкулеза.

Isonicotinoyl hydrazones of pyridoxine derivatives: synthesis and antimycobacterial activity

A series of novel isonicotinoyl hydrazones based on pyridoxine (vitamin B6) were synthesized. The synthesized compounds were evaluated for their antimycobacterial activity on M. tuberculosis H37Rv strain. The most potent compound 13 showed good activity on H37Rv strain and on clinical isolates of M. tuberculosis with multidrug-resistant tuberculosis (TB) profile included first- and second-line drugs. Cytotoxicity studies of compound 13 on human embryonic kidney cells, human liver, human mesenchymal stem cells, and human embryonic lung cells in vitro demonstrated it is 2–3 times less toxicity then isoniazid and 1.5–2 less toxicity than ethambutol and moxifloxacin. Compound 13 showed weak complexation with Fe3+ ions, low acute toxicity (LD50 > 2000 mg/kg per os on mice) and the identical to isoniazid and significantly better than ethambutol and moxifloxacin efficacious in the mouse model of drug-sensitive (H37Rv) TB. These facts make him a promising candidate for future developments of antitubercular drugs. [Figure not available: see fulltext.