Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology7610.36233/0372-9311-2016-4-105-115REVIEWSОБЗОРЫSYNTHETIC BIOLOGY AS AN INSTRUMENT FOR DEVELOPMENT OF INNOVATIVE VACCINES FOR PROPHYLAXIS OF BACTERIAL INFECTIONSСИНТЕТИЧЕСКАЯ БИОЛОГИЯ КАК ИНСТРУМЕНТ ДЛЯ РАЗРАБОТКИ ИННОВАЦИОННЫХ ВАКЦИН ДЛЯ ПРОФИЛАКТИКИ БАКТЕРИАЛЬНЫХ ИНФЕКЦИЙKolesnikovA. V.КолесниковА. В.
Russian Federation
KozyrA. V.КозырьА. В.
Russian Federation
ShemyakinL. G.ШемякинИ. Г.
Russian Federation
LisitskayaLA. ..ЛисицкаяЛЛ. ..
Russian Federation
MarinM. A.МарьинМ. А.
Russian Federation
RyabkoA. K.РябкоА. К.
Russian Federation
DyatlovLA. ..ДяпыовИ. А.
Russian Federation
State Scientific Centre of Applied Microbiology and BiotechnologyГНЦ прикладной микробиологии и биотехнологииInstitute of Engineering ImmunologyИнститут инженерной иммунологии2808201693410511510042019Copyright ©; 2016, Kolesnikov A.V., Kozyr A.V., Shemyakin L.G., Lisitskaya L..., Marin M.A., Ryabko A.K., Dyatlov L...Copyright ©; 2016, Колесников А.В., Козырь А.В., Шемякин И.Г., Лисицкая Л..., Марьин М.А., Рябко А.К., Дяпыов И.А.2016Kolesnikov A.V., Kozyr A.V., Shemyakin L.G., Lisitskaya L..., Marin M.A., Ryabko A.K., Dyatlov L...Колесников А.В., Козырь А.В., Шемякин И.Г., Лисицкая Л..., Марьин М.А., Рябко А.К., Дяпыов И.А.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/76

For many decades, live vaccines remain the most effective means for prophylaxis of bacterial infections. Until recently, the main source of vaccine strains were empirically selected bacteria, virulence of which was attenuated due to natural mutations. Despite effectiveness of such vaccines against a number of infections, use of attenuated strains for many pathogens either does not induce sufficient protection, or is unsafe. Traditional technologies of vaccine creation frequently have low effectiveness with the lack of pronounced «protective» antigens in the pathogen. Methods of rational construction of live vaccines have received development in the recent years, based on methodology of synthetic biology. Contribution of synthetic biology into creation of vaccines is not limited to use of means of bioinformatics and construction of optimized DNA fragments, but also includes coordinated adjustments to various components of the bacterial genome, creation of vector strains, inclusion of altered immunogens and immune system activators into them, search and design of immunogens in silico and much more. Methodologies of synthetic biology allow to combine various engineering ideas and building blocks, obtained during creation and modification of various prophylaxis, therapeutic and bioengineering systems for production of microorganisms with qualitatively novel and programmable properties, and in perspective - rapidly create vaccines «on demand».

На протяжении многих десятилетий, живые вакцины остаются наиболее эффективным средством профилактики бактериальных инфекций. Основным источником вакцинных штаммов до последнего времени являлись эмпирически отобранные бактерии, вирулентность которых была аттенуирована в силу природных мутаций. Несмотря на эффективность таких вакцин в отношении ряда инфекций, для многих патогенов использование аттенуированных штаммов либо не обеспечивает достаточной защиты, либо является небезопасным. Традиционные технологии создания вакцин зачастую малоэффективны при отсутствии у патогена выраженных «протективных» антигенов. В последние годы развитие получили методы рационального конструирования живых вакцин на основе методологий синтетической биологии. Вклад синтетической биологии в создание вакцин не ограничивается использованием средств биоинформатики и конструированием оптимизированных фрагментов ДНК, а включает в себя скоординированные изменения различных компонентов бактериального генома, создание векторных штаммов, включение в них видоизмененных иммуногенов и активаторов иммунной системы, поиск и дизайн иммуногенов in silico и многое другое. Методологии синтетической биологии позволяют объединить различные инженерные идеи и строительные блоки, полученные при создании и модификации различных профилактических, терапевтических и биоинженерных систем для получения микроорганизмов с качественно новыми и программируемыми свойствами, а в перспективе - в короткие сроки создавать вакцины «по требованию».

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