April 2021
clinical initiatives, research and current updates in treatment
mRNA Vaccines – A New Era in Vaccinology Ben Evans, Priya Iyer, Icon River City Pharmacy The COVID-19 pandemic has seen an unprecedented acceleration in vaccine development. With it has come the approval of the first mRNAbased therapeutics in the form of the Moderna and Pfizer vaccines. Although considered novel in design, these represent the culmination of decades of research into the utilisation of mRNA as a viable vaccine technology. Vaccination relies on the ability of the immune system to produce an antibody mediated immune response against foreign pathogens such as bacteria and viruses. The portion of a pathogen that is recognised by the immune system is referred to as an antigen. An antigen-presenting cell (APC) is an immune cell that stimulates the initial immune response by phagocytosing (engulfing) a pathogen and digesting it to form antigens. These antigens are then transported to the surface of the APC where they serve as an indicator to other immune cells. In traditional vaccines, antigens are introduced by administering an attenuated (weakened) or inert version of the causative organism, its products, or a synthetic substitute. This exposes the body to the antigen and stimulates the production of targeted antibodies without inducing the disease.1 mRNA vaccines utilise this same exact principle, with the major difference being that the vaccine carries
information that triggers our bodies own protein production machinery to produce the antigen of interest.2 This technology led to the rapid development of the COVID-19 vaccine. In the case of the SARS-Cov-2 virus, the antigen of interest is the “spike” surface protein that is a feature unique to coronaviruses.3 By administering an mRNA strand that has been engineered with the instructions to produce this spike protein, the immune system is triggered to produce antibodies directed against the protein, without risking exposure to the virus itself. To understand how this is achieved, it is important to understand what mRNA is, and how it functions.
What is mRNA? mRNA or messenger RNA is an intermediate molecule involved in normal protein synthesis. It is responsible for carrying genetic information encoded in our DNA which guides the production of proteins necessary for normal biological functions. This is achieved via a twostep process known as transcription and translation. Transcription occurs within the nucleus of cells, where portions of DNA unwind and are copied onto an mRNA strand. Following this process, the mRNA exits the nucleus and is presented to ribosomes located within the cytoplasm, where the instructions are translated into a corresponding protein that is used for a particular function.4 (See Figure 1)
Figure 1: https://medlineplus.gov/genetics/ understanding/howgeneswork/makingprotein/ 4
The ability of mRNA to encode for proteins makes it a powerful potential therapeutic tool. mRNA is a noninfectious, non-integrating platform with no potential risk of infection or DNA mutations. Additionally, mRNA is degraded by normal cellular processes and therefore has a safe risk profile.5 Not only is mRNA safe, but producing vaccines in this way is faster than traditional methods of vaccine production.6
mRNA vaccine production Utilising mRNA as a therapeutic tool has been the focus of research for several decades now. However, translating this theory into clinical practice has proved challenging. An early limiting factor in the development of mRNA-based therapeutics was that “naked” mRNA is rapidly broken down within the body. Continued on page 2