УДК  615.371:577.215.3
DOI: https://doi.org/10.52540/2074-9457.2025.2.77
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Н. С. Голяк, В. М. Царенков, О. А. Сушинская, О. Г. Сечко, С. С. Мальчëнкова

ДОСТИЖЕНИЯ В ОБЛАСТИ РАЗРАБОТКИ ВАКЦИН НА ОСНОВЕ мРНК

Белорусский государственный медицинский университет, г. Минск, Республика Беларусь

 

В статье описывается структура естественной эукариотической и синтетической мРНК, влияние модификации составных частей синтетической мРНК на иммуногенность, повышение стабильности и эффективности трансляции. Представлены ключевые открытия и достижения, способствующие появлению мРНК-вакцин как лекарственных препаратов. Описаны этапы производства мРНК вакцин, а также структура липидных наночастиц, как единственно одобренная для клинического использования система доставки мРНК. Представлена краткая характеристика двух первых одобренных мРНК вакцин для профилактики Covid-19: Comirnaty® и Spikevax®. Показано, что обе вакцины имеют оптимизированную структуру мРНК и кодируют S-белок mut, содержащий две мутации K986P и V987P (P2 S, которые гарантируют, что S-белок остается в антигенно оптимальной конформации до слияния. Обе вакцины доставляются в клетки с помощью липидных наночастиц, состоящих из 50% в молярном соотношении ионизированных липидов, 38,5% холестерина, 10% дистеарилфосфотидилхолина и 1,5% пэгилированного липида. Производители используют разные ионизированные и пегилированные липиды. Обе вакцины представляют собой стерильную белую дисперсию, но состав вспомогательных веществ отличается. Одобренные мРНК-вакцины требуют хранения при низких (-20 °C) Spikevax® или сверхнизких температурах (-70 °C) Comirnaty®. В качестве криопротектора используется сахароза. Описаны данные по безопасности применения зарегистрированных вакцин для профилактики Covid-19. Основными нежелательными реакциями являются спайкопатия, неврологические нарушения, возникновение аутоимммунных заболеваний. Показаны перспективы повышения стабильности мРНК вакцин за счет лиофилизации и получения кольцевых мРНК.

Ключевые слова: мРНК, вакцины, структура мРНК, липидные наночастицы (ЛНЧ), катионные липиды, ионизированные липиды, пегилированные липиды, лиофилизированные мРНК-вакцины, самоамплифицирующиеся мРНК-вакцины, кольцевые мРНК-вакцины, безопасность, эффективность.

 

SUMMARY

S. Golyak, V. M. Tsarenkov, O. A. Sushinskaya, O. G. Sechko, S. S. Malchenkova

ADVANCES IN THE DEVELOPMENT OF MRNA-VACCINES

The article describes the structure of natural eukaryotic and synthetic mRNA, the effect of modification of the components of synthetic mRNA on immunogenicity, increasing stability and translation efficiency. Key discoveries and achievements that contribute to the emergence of mRNA vaccines as drugs are presented. The stages of mRNA vaccine production are described, as well as the structure of lipid nanoparticles as the only mRNA delivery system approved for clinical use. A brief description of the first two approved mRNA vaccines for the prevention of Covid-19: Comirnaty® and Spikevax® is presented. Both vaccines have been shown to have an optimized mRNA structure and encode the S protein mut containing two mutations, K986P and V987P (P2 S, which ensure that the S protein remains in an antigenically optimal conformation prior to fusion. Both vaccines are delivered to cells using lipid nanoparticles composed of 50% molar ionized lipids, 38.5% cholesterol, 10% distearylphosphatidylcholine and 1.5% pegylated lipid. The ionized and pegylated lipids used by the manufacturers differ. Both vaccines are a sterile white dispersion, but the excipient composition differs. The approved mRNA-vaccines require storage at low (-20 °C) Spikevax® or ultra-low temperatures (-70 °C) Comirnaty®. Sucrose is used as a cryoprotectant. The safety data for the use of registered vaccines for the prevention of Covid-19 are described. The main adverse reactions are adhesion disease, neurological disorders, and the occurrence of autoimmune diseases. The prospects for increasing the stability of mRNA vaccines through lyophilization and obtaining circular mRNA are shown.

Keywords: mRNA, vaccines, mRNA structure, lipid nanoparticles (LNPs), cation lipids, ionized lipids, pegylated lipids, lyophilized mRNA vaccines, self-amplifying mRNA-vaccines, safety, efficacy

 

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Голяк Н. С.

Поступила 10.06.2025 г.