Journal of Vaccine Research 2024, Vol.14, No.3, 95-106 http://medscipublisher.com/index.php/jvr 97 2.3 Pre-COVID-19 applications Before the COVID-19 pandemic, mRNA vaccines were already being investigated for a range of infectious diseases and therapeutic applications. Early clinical trials focused on viral infections such as influenza, rabies, and Zika, demonstrating the versatility and potential of mRNA vaccines (Pardi et al., 2018). Moreover, mRNA technology was explored for cancer immunotherapy, where it was used to encode tumor-associated antigens to stimulate an anti-tumor immune response (Maruggi et al., 2019). These pre-COVID-19 efforts provided critical insights and established a foundation for the rapid development and deployment of mRNA vaccines during the pandemic. The development of mRNA vaccines before the COVID-19 era highlighted their potential to address a wide array of medical challenges, setting the stage for their pivotal role in the global response to the pandemic. The pre-existing research and technological infrastructure were instrumental in the swift creation and approval of mRNA-based COVID-19 vaccines, showcasing the readiness of this platform to tackle emergent health crises (Kim et al., 2021). 3 Mechanism of Action of mRNA Vaccines 3.1 Structure and composition of mRNA vaccines mRNA vaccines are composed of a few critical components that ensure their stability and functionality. The primary element is the mRNA molecule itself, which encodes the antigen of interest. This mRNA is synthesized in vitro using a DNA template and includes modifications such as a 5' cap and a poly(A) tail to enhance its stability and translation efficiency (Gote et al., 2023). Additionally, the mRNA is often modified with pseudouridine or other nucleoside analogs to reduce its immunogenicity and increase its half-life within the host cells (Pardi et al., 2020). The mRNA is encapsulated in lipid nanoparticles (LNPs), which serve multiple purposes: they protect the mRNA from degradation, facilitate its uptake by cells, and promote endosomal escape into the cytoplasm where translation occurs (Hassett et al., 2019). LNPs are typically composed of ionizable lipids, cholesterol, phospholipids, and polyethylene glycol (PEG)-lipid, which together form a stable and efficient delivery vehicle (Jackson et al., 2020). 3.2 Cellular mechanisms The immune response generated by mRNA vaccines is typically strong and includes the activation of memory cells, which provide long-lasting immunity. This comprehensive immune activation mimics the body's natural response to infection, resulting in effective protection against the target pathogen (Iavarone et al., 2017). Figure 2 details the entire process of mRNA from transcription to immune activation. Figure 2 Process of In Vitro transcription of mRNA and innate immune activation (Adapted from Xu et al., 2020) Image Caption: A describes the in vitro transcription of mRNA using a DNA template containing an antigen-coding sequence, producing single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) products; B illustrates how mRNA enters the host cell
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