Bulletin of the Russian Military Medical AcademyBulletin of the Russian Military Medical AcademyВестник Российской военно-медицинской академии1682-73922687-1424Eco-Vector6509510.17816/brmma65095ReviewsОбзорыReview ArticleMolecular aspects of creating vaccines for the prevention of poisoning ribosome-inactivating proteins of plant origin: current situation, problems of vaccine developmentМолекулярные механизмы создания вакцин для профилактики отравлений рибосомингибирующими белками растительного происхождения: современное состояние, перспективы разработки и развития средств иммунопрофилактики5084-2723MyasnikovVadim A.МясниковВадим Александрович
Russian Federation

candidate of medical sciences

кандидат медицинских наук

letto2004@inbox.ru7279-7055StepanovAlexander V.СтепановАлександр Валентинович
Russian Federation

doctor of medical sciences, professor

доктор медицинских наук, профессор

letto2004@inbox.ruhttps://orcid.org/0000-0002-3874-6954551956853002070-7250MitevaOlga A.МитеваОльга Анатольевна
Russian Federation

researcher

научный сотрудник

letto2004@inbox.ru8503-0338NikishinAlexander S.НикишинАлександр Сергеевич
Russian Federation

researcher

научный сотрудник

letto2004@inbox.ru5807-9998GogolevskyAlexander S.ГоголевскийАлександр Сергеевич
Russian Federation

doctor of medical sciences

доктор медицинских наук

letto2004@inbox.ru4900-9032Al-ShehadatRuslan I.Аль-ШехадатРуслан Исмаилович
Russian Federation

candidate of biological sciences

кандидат биологических наук

letto2004@inbox.ruState Scientific-research Test Institute of Military MedicineГосударственный научно-исследовательский испытательный институт военной медицины МО РФ150620212322192281404202101062021Copyright ©; 2021, Myasnikov V.A., Stepanov A.V., Miteva O.A., Nikishin A.S., Gogolevsky A.S., Al-Shehadat R.I.Copyright ©; 2021, Мясников В.А., Степанов А.В., Митева О.А., Никишин А.С., Гоголевский А.С., Аль-Шехадат Р.И.2021Myasnikov V.A., Stepanov A.V., Miteva O.A., Nikishin A.S., Gogolevsky A.S., Al-Shehadat R.I.Мясников В.А., Степанов А.В., Митева О.А., Никишин А.С., Гоголевский А.С., Аль-Шехадат Р.И.http://creativecommons.org/licenses/by-nc-nd/4.0https://journals.eco-vector.com/1682-7392/article/view/65095

This article reviews the current understanding of the mechanism of action of the toxin, the clinical effects of ricin and abrin intoxication and how these relate to current and continuing prospects for vaccine development. The threat of bioterrorism worldwide has accelerated the demand for the development of therapies and vaccines against the ribosome-inactivating proteins. The diverse and unique nature of these toxins poses a challenge to vaccinologists. This paper will review the mechanism of toxicity and vaccines development to protect against the highly toxic plant-derived ribosomal toxins. Vaccine development is further complicated by the fact that as bioterrorism agents, abrin and ricin would most likely be disseminated as aerosols supplies. Our understanding of the mechanisms by which these toxins cross mucosal surfaces, and importance of mucosal immunity in preventing toxin uptake is only rudimentary. Research is now aimed at developing recombinant, attenuated vaccines based on a detailed understanding of the molecular mechanisms by which these toxins function. The evolution of the development of specific immunoprophylaxis of acute ricin poisoning from native toxoid to genetically engineered subunit vaccines based on the method of targeted mutagenesis is traced. The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine. These vaccines are discussed in the context of the toxicity and structure of ricin. In this review we summarize ongoing efforts to leverage recent advances in the design and use of vaccines.

Проанализированы основные тенденции и перспективы создания высокоэффективных иммунобиологических лекарственных препаратов для профилактики и терапии острых поражений рибосом-ингибирующими токсинами растительного происхождения, рицина и абрина. Обобщены данные, описывающие представления о базовых молекулярных механизмах и природе взаимодействий токсин-антитело, определяющих способность антител нейтрализовать риботоксичные растительные лектины, и лежащие в основе создания успешных кандидатных вакцинных препаратов. Приведены данные, характеризующие поражающие эффекты растительных риботоксинов на молекулярном уровне, определяющие выбор перспективных направлений разработки средств иммунопрофилактики отравлений. Суммированы результаты исследований, направленных на понимание молекулярных механизмов, обеспечивающих формирование протективного иммунитета против нативных риботоксинов, и их отдельных субъединиц. Прослежена эволюция создания средств иммунопрофилактики острых отравлений рицином: от нативного анатоксина до генно-инженерных субъединичных вакцин, созданных на основе метода таргетного мутагенеза. Показаны основные этапы создания, исследования и испытания современных образцов вакцин-кандидатов, разработанных для профилактики ингаляционных и пероральных отравлений рицином. Обобщены результаты исследований, включающие данные, которые были получены в ходе доклинических испытаний, демонстрирующих высокую протективную активность современных иммунобиологических лекарственных препаратов против отравления растительными лектинами, ингибирующими синтез белка в клетке. Приведены подходы к усилению иммуногенности субъединичных вакцин против рибосомингибирующих белков растительного происхождения. Выявлены основные проблемные моменты при создании и применении вакцинных препаратов, определены основные тенденции и перспективы их совершенствования.

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