mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-SAE-2320mimmun-2320Research ArticleОБЗОРЫREVIEWSЭффективность и безопасность РНК-вакцин: что известно на сегодняшний деньSafety and efficacy of RNA vaccines: State of the artБлаговА. В.BlagovA. V.

Благов Александр Владимирович — аналитик отдела анализа  и прогнозирования медико-биологических рисков здоровью.

119435, Москва, ул. Погодинская, 10, стр. 1.

Analyst, Department of Analysis and Prognosis of Biomedical Health Risks, Center for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency.

119435, Moscow, Pogodinskaya str., 10, bldg 1.

ABlagov@cspmz.ruhttps://orcid.org/0000-0002-5932-1744БукаеваА. А.BukaevaA. A.

Букаева Анна Алексанровна — аналитик отдела анализа и прогнозирования медико-биологических рисков здоровью.

119435, Москва, ул. Погодинская, 10, стр. 1.

Analyst, Department of Analysis and Prognosis of Biomedical Health Risks, Center for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency.

119435, Moscow, Pogodinskaya str., 10, bldg 1.

abukaeva@cspmz.ruhttps://orcid.org/0000-0001-9495-0266МакаровВ. В.MakarovV. V.

Макаров Валентин Владимирович — кандидат биологических наук, начальник отдела анализа и прогнозирования медико-биологических рисков здоровью.

119435, Москва, ул. Погодинская, 10, стр. 1.

Head, Department of Analysis and Prognosis of Biomedical Health Risks, Center for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency.

119435, Moscow, Pogodinskaya str., 10, bldg 1.

makarov@cspmz.ruhttps://orcid.org/0000-0001-9218-3331БочкаеваЗ. В.BochkaevaZ. V.

Бочкаева Занда Владимировна — кандидат биологических наук, аналитик отдела анализа и прогнозирования медико-биологических рисков здоровью.

119435, Москва, ул. Погодинская, 10, стр. 1.

Тел.: 8 (495) 540-61-74 (доб. 1134).

Zanda V. Bochkaeva - Analyst, Department of Analysis and Prognosis of Biomedical Health Risks, Center for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency.

119435, Moscow, Pogodinskaya str., 10, bldg 1.

Phone: 7 (495) 540-61-74 (acc. 1134).

ZBochkaeva@cspmz.ruЦентр стратегического планирования и управления медико-биологическими рисками здоровью ФМБА РоссииРоссияCenter for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological AgencyRussian Federation20211511202123510171030Copyright © Благов А.В., Букаева А.А., Макаров В.В., Бочкаева З.В., 20212021Благов А.В., Букаева А.А., Макаров В.В., Бочкаева З.В.Blagov A.V., Bukaeva A.A., Makarov V.V., Bochkaeva Z.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2320

Разработку РНК-вакцин от COVID-19, затребовавшую всего несколько месяцев на все фазы клинических испытаний и регистрационные процедуры и увенчавшуюся успешным выводом на рынок, можно назвать одним из главных прорывов фармакологии за последний год. Несмотря на все кажущиеся на первый взгляд неоспоримыми преимущества, с момента открытия в 1993 г. до прошлого года ни одна из разрабатываемых РНК-вакцин не вышла к III фазе клинических испытаний.

Считается, что первый опыт успешного использования вакцин на основе мРНК был еще в 90-х годах прошлого века, когда было обнаружено, что вакцинирование мышей липосомами с мРНК, кодирующей антиген, инициировало формирование иммунного ответа у животных. Однако в те годы метод не нашел применения по причине токсичности используемых липидов. В последующем было предпринято большое количество попыток разработки вакцин от других вирусных инфекций, включая вирус Зика, вирус денге, вирус Эбола, цитомегаловирус, вирус гриппа и т.д. Несмотря на важность профилактики этих заболеваний, разработка вакцинного препарата является довольно длительным процессом, не всегда увенчивающимся успехом. Однако пандемия COVID-19 стала большим стимулом для ускорения процесса разработки мРНК-вакцин.

На момент написания обзора в мире зарегистрированы только две вакцины на основе мРНК, обе для профилактики COVID-19 — BNT162b2 и мРНК-1273. Их эффективность и безопасность продолжают активно изучать до сих пор. Более того, не прошло и года с начала пандемии, как появились новые штаммы коронавируса SARS-CoV-2, эффективность вакцин против которых оказалась ниже, чем против референсного варианта патогена. Учитывая, что в мире с большой скоростью распространяются три новых штамма SARS-CoV-2: «британский», «африканский» и «бразильский», уже известны результаты первых оценок эффективности препаратов против них. Как и предполагалось, основываясь на мутациях этих штаммов, вакцины BNT162b2 и мРНК-1273 сохраняют эффективность против «британского» штамма, однако их защитные свойства сильно ослаблены против «африканского».

В данном обзоре рассмотрены принцип действия и способ доставки в клетки молекул мРНК, описаны некоторые из разработанных ранее, но не зарегистрированных РНК-вакцин и результаты, полученные при их исследовании. Кроме того, в обзоре обсуждаются актуальные на момент написания данные об эффективности и безопасности зарегистрированных для профилактики COVID-19 РНК-вакцин.

This review describes principles of action and the method of delivery of mRNA molecules into cells, as well as some of developed RNA vaccines and the results obtained in their study, though they have not been authorized for use yet. In addition, the review discusses efficacy and safety proved for RNA vaccines registered for COVID-19 prevention at the time of writing. The development, clinical trials and market launch of RNA vaccines for mass immunization in a few months can be considered one of the major breakthroughs in pharmacology over the past year. Despite of all seemingly indisputable advantages, none of RNA vaccines had reached Phase III of clinical trials since the moment of its discovery in 1993 until last year. The first experience of the successful use of mRNA vaccines was back in the 90s of the last century, when vaccination of mice with liposomes encoding an antigen-encoding mRNA was found to initiate specific immune response in mice. However, in these years, the method did not find application, due to the toxicity of lipids used. Subsequently, a large number of attempts have been made to develop vaccines against other viral infections, including Zika virus, Dengue virus, Ebola virus, cytomegalovirus, influenza virus and others. Despite the importance for preventing the spread of these diseases, the development of a vaccine preparation is a rather lengthy process, and final success is not guaranteed. However, the COVID-19 pandemic has become speeded the development of mRNA vaccines up.

At the time of writing the review, two mRNA-based vaccines have been registered only in the world, both, BNT162b2 and mRNA-1273, were against COVID-19. Their effectiveness and safety are still actively studied. Moreover, it took less than a year for new strains of SARS-CoV-2 to appear, and the efficiency of vaccines against them was found to be lower than against the reference pathogen variant. Considering that the three new strains of SARS-CoV-2, “British”, “African” and “Brazilian”, are rapidly spreading in the world, the first results of efficiency evaluation of vaccines against them have already been published. One may expect that, considering mutations in these strains, the BNT162b2 and mRNA-1273 vaccines will remain effective against the “British” strain, but their protective properties are greatly weakened against the “African” variant.

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The authors declare that there are no conflicts of interest present.