Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology1583810.36233/0372-9311-404psdxzrREVIEWSОБЗОРЫReview ArticleLive attenuated COVID-19 vaccines: approaches to development and prospects for clinical useЖивые аттенуированные вакцины против COVID-19: подходы к разработке и перспективы клинического примененияhttps://orcid.org/0000-0002-6417-3301KorchevayaEkaterina R.КорчеваяЕкатерина Романовна
Russian Federation

junior researcher, Laboratory of applied virology, Department of Virology

м.н.с., лаб. прикладной вирусологии

c.korchevaya@gmail.comhttps://orcid.org/0000-0001-8428-4482GrachevaAnastasiia V.ГрачеваАнастасия Вячеславовна
Russian Federation

researcher, Laboratory of applied virology, Department of Virology

н.с., лаб. прикладной вирусологии

c.korchevaya@gmail.comhttps://orcid.org/0000-0001-5384-9866DyakovIlya N.ДьяковИлья Николаевич
Russian Federation

PhD (Biol.), Head of Laboratory of biosynthesis of immunoglobulins, Department of Virology

к.б.н., зав. лаб. биосинтеза иммуноглобулинов

c.korchevaya@gmail.comhttps://orcid.org/0000-0001-5808-2246ZverevVitaly V.ЗверевВиталий Васильевич
Russian Federation

D. Sci. (Biol.), Prof., Academician of RAS, scientific director

д.б.н., профессор, академик РАН, научный руководитель

c.korchevaya@gmail.comhttps://orcid.org/0000-0001-7385-5083FaizuloevEvgeny B.ФайзулоевЕвгений Бахтиерович
Russian Federation

PhD (Biol.), Head, Laboratory of applied virology

к.б.н., зав. лаб. прикладной вирусологии

c.korchevaya@gmail.comI. Mechnikov Research Institute for Vaccines and SeraНаучно-исследовательский институт вакцин и сывороток имени И.И. МечниковаRussian Medical Academy of Continuous Professional EducationРоссийская медицинская академия непрерывного профессионального образования1107202310032252361107202311072023Copyright ©; 2023, Korchevaya E.R., Gracheva A.V., Dyakov I.N., Zverev З.V., Faizuloev E.B.Copyright ©; 2023, Корчевая Е.Р., Грачева А.В., Дьяков И.Н., Зверев В.В., Файзулоев Е.Б.2023Korchevaya E.R., Gracheva A.V., Dyakov I.N., Zverev З.V., Faizuloev E.B.Корчевая Е.Р., Грачева А.В., Дьяков И.Н., Зверев В.В., Файзулоев Е.Б.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/15838

Although WHO declared an end to the pandemic, COVID-19 remains a significant public health concern worldwide. Modern vaccines often induce either only humoral or only cellular immunity. Furthermore, new emergent epidemiologically significant SARS-CoV-2 variants and their spread considerably reduce the effectiveness of preventive vaccination. Therefore, there is an urgent need to improve the existing vaccines against COVID-19. One of the promising approaches to the solution of the problem is creation of a "universal" vaccine that would have a cross-protective activity against different antigenic variants of the virus. In this respect, the development of live attenuated vaccine is of special interest, as it can activate not only humoral, but also cell-mediated components of immunity, providing long-term immune response and cross-protection against different variants of the virus.

This review highlights the existing approaches to producing attenuated SARS-CoV-2 strains and gives an assessment of their prospects for clinical use. Some researchers use methods of genetic engineering and reverse genetics such as site-directed mutagenesis and codon deoptimization for virus attenuation. Others tend to use traditional approaches focusing on producing virus mutants through extended passaging in cell culture under selective conditions. The gained experience demonstrates great prospects for development of highly effective live-attenuated vaccine against COVID-19.

Несмотря на объявленное ВОЗ завершение пандемии, COVID-19 остаётся актуальной проблемой здравоохранения во всём мире. Современные вакцины зачастую формируют либо только гуморальный, либо только клеточный иммунитет. Кроме того, появление и распространение новых эпидемиологически значимых вариантов SARS-CoV-2 значительно снижает эффективность вакцинопрофилактики. Всё это требует совершенствования существующих вакцин против COVID-19. Одним из возможных подходов к решению данной проблемы является создание «универсальной» вакцины, обладающей перекрёстной протективной активностью в отношении разных антигенных вариантов вируса. В связи с этим представляет интерес разработка живой аттенуированной вакцины, способной активировать не только гуморальное, но и клеточное звено иммунитета, обеспечивая продолжительный иммунный ответ и перекрёстную защиту от разных вариантов вируса.

В данном обзоре рассматриваются реализованные подходы к получению аттенуированных штаммов SARS-CoV-2 и оценивается потенциал их клинического применения. Одни авторы для аттенуации вируса используют методы генной инженерии и обратной генетики, такие как сайт-направленный мутагенез и деоптимизация кодонов. Другие используют традиционный подход, направленный на получение мутантов вируса путём длительного пассирования в культуре клеток в селективных условиях. Накопленный на сегодняшний день опыт показывает большой потенциал создания высокоэффективной живой аттенуированной вакцины против COVID-19.

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