PANDEMIC
A Look into Conventional and mRNA Vaccines in Application to COVID-19 By Annie Chen, Biochemistry Major, 2021
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accines help the body to safely build immunity against disease by imitating an infection. The use of vaccines has drastically prevented infections including, but not limited to, measles, chickenpox, hepatitis B, tetanus, polio, and yearly influenza. The conventional methods to develop vaccines include using (1) live, attenuated pathogens that use a weakened version of the living virus or bacteria to mimic the actual infection within individuals with healthy immune systems.4 Several examples of live, attenuated vaccines include those for measles, mumps, rubella, and chickenpox. (2) Inactivated pathogens also fight viruses and bacteria by deactivating the germ during the process of designing the vaccine; however, this method requires multiple doses to maintain immunity.4 An example of inactivated vaccines is used to prevent polio. (3) Subunit vaccines fight against viruses and bacteria by including essential antigens, rather than the entire parts of virus or bacteria, to mimic infection with fewer vaccine side effects.4 An example of a subunit vaccine includes the DTaP vaccine to prevent pertussis (whooping cough). (4) Finally, conjugated vaccines fight against bacteria by connecting or conjugating to a bacteria’s polysaccharide coating to allow the immune system to react.4 A conjugated vaccine was developed to prevent Haemophilus influenzae type B (Hib). Although conventional vaccines have prevented certain types of infections, there are still obstacles to create vaccines that can prevent infectious pathogens that evade the immune system, can be applicable to non-infectious diseases such as cancer, and can be produced for rapid and large-scale use.3 Certainly, with the COVID-19 pandemic, there has been a rapid search and development of an effective vaccine against the spike protein, which is found on the surface of the virus and allows it to enter human cells. Recent research has made strides in nucleic acid therapeutic interventions, including DNA-based and protein-based approaches, as emerging alternatives to conventional vaccines.3 Notably, the advent of
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messenger RNA (mRNA) for vaccine development provides promising safety, efficacy, and production benefits compared to conventional vaccines. Messenger RNA is a single-stranded molecule that is transcribed (copied) from a strand of DNA and translated into proteins in the cytoplasm. In the first step, a template strand on the parental double-stranded DNA containing the genetic code is transcribed into single-stranded mRNA in the nucleus of the cell. Next, the mRNA travels from the nucleus to the cytoplasm where protein-synthesizing machinery, known as ribosomes, begin to “read” the RNA genetic code in groups of three nucleotides (known as codons) and creates proteins based on the genetic information. Finally, the cell carries the protein to designated locations where the protein performs its function.
The process of creating messenger RNA (mRNAs) and Proteins. Photo courtesy of Moderna. Ultimately, it is the synthesis of proteins from mRNA instructions separates the benefits of mRNAs from conventional methods of vaccine development, like using live and attenuated or inactivated pathogens. The benefits of an mRNA vaccine include (1) no risk of infection with an mRNA vaccine as mRNA is noninfectious and non-integrating, but rather works by providing instructions to our cells to make proteins in the cytoplasm; (2) normal cellular degradation of mRNA which allows researchers to regulate the in vivo half-life of mRNAs through different delivery methods and avoid metabolic toxicity; (3) stability and high
