mRNA-Based Vaccines – Challenges in the Manufacturing Process

Abstract

Pandemija COVID-19 je poslužila kao katalizator za ubrzani razvoj i primenu iRNK vakcina, ističući njihovu ključnu ulogu u suzbijanju infektivnih bolesti. Brzina razvoja iRNK vakcina, uz istovremeno ispunjavanje strogih bezbednosnih standarda, potvrdila je superiornost ove tehnologije u odgovoru na globalne zdravstvene izazove. U cilju postizanja optimalne efikasnosti, stabilnosti i bezbednosti, primenjuju se napredne tehnike, uključujući upotrebu modifikovanog uridina i/ili samoreplikujuće iRNK, čime se obezbeđuje adekvatan i dugotrajan imunski odgovor, uz usklađenost sa regulatornim i kliničkim zahtevima. Takođe, jedna od ključnih prednosti ove vakcinalne platforme je brzina i fleksibilnost proizvodnje u odnosu na tradicionalne vakcine, pri čemu standarizovani procesi i modularna priroda omogućavaju jednostavnu adaptaciju na nove varijante patogena, bez potrebe za značajnim izmenama proizvodnog postupka. Proizvodni postupak počinje dizajniranjem i proizvodnjom plazmidne DNK, koja se nakon prečišćavanja linearizuje, a zatim koristi kao matrica za sintezu iRNK molekula u reakciji in vitro transkripcije. Sintetisana iRNK mora proći kroz nekoliko faza prečišćavanja kako bi se eliminisali kontaminanti poput DNK, proteina i dr. Sledeći i najznačajni korak za stabilnost je enkapsulaciju iRNK, najčešće pomoću lipidnih nano-čestica (LNP) ili polimernih nanočestica, čime se omogućava efikasna dostava do ciljnih ćelija. Svi koraci proizvodnje su u skladu sa regulatornim standardima i praćeni strogim testovima kontrole kvaliteta, kako bi se osigurala bezbednost, efikasnost i konzistentnost vakcine. Trenutno su u kliničkim ispitivanjima iRNK vakcine protiv različitih virusnih i bakterijskih infekcija. Osim toga, iRNK tehnologija pokazuje veliki potencijal za personalizovanu terapiju, uključujući lečenje retkih genetskih i autoimunih bolesti, kao i razvoj individualizovanih onkoloških terapija.The rapid development of mRNA vaccines, while simultaneously meeting safety standards, has confirmed the superiority of this technology in responding to global health challenges, especially during the COVID-19 pandemic. To achieve optimal efficacy, stability, and safety of mRNA vaccines, advanced techniques such as the use of modified uridine and/or self-amplifying mRNA are employed, ensuring a robust and durable immune response while maintaining compliance with regulatory and clinical requirements. Additionally, one of the key advantages of mRNA vaccine platform is the speed and flexibility of production compared to traditional vaccines. Standardized processes and the modular nature of mRNA technology allow for easy adaptation to new pathogen variants without significant modifications to the manufacturing process. The production process begins with the design and synthesis of plasmid DNA, which is linearized and then used as a template for synthesizing mRNA molecules via in vitro transcription. The synthesized mRNA undergoes multiple purification steps to remove contaminants such as residual DNA, proteins, and other impurities. The next and most crucial step for stability is mRNA encapsulation, typically using lipid nanoparticles (LNPs) or polymeric nanoparticles, enabling efficient delivery to target cells. All manufacturing steps comply with regulatory standards and are accompanied by rigorous quality control testing to ensure the safety, efficacy, and consistency of the vaccine. Currently, mRNA vaccines are undergoing clinical trials for various viral and bacterial infections. Furthermore, mRNA technology holds great potential for personalized therapies, including the treatment of rare genetic and autoimmune diseases, as well as the development of individualized cancer therapies