Written by Josephine Chen
Edited by Jacqueline Cho
The first COVID-19 vaccines approved and authorized for use in the United States were messenger RNA (mRNA) vaccines, but what exactly is an mRNA vaccine?
Although there are different types of vaccines, each with its own mechanism of action in the human body, all vaccines stimulate the immune system to defend itself against harmful pathogens. One familiar example is the influenza vaccine, which uses a weakened or deactivated form of the influenza virus. After this deactivated virus is introduced into the body, the immune system can recognize the specific proteins found on the surface of the virus, called antigens. The immune system can t
hen develop antibodies that protect against the virus by recognizing and attaching to the pathogen, allowing it to be destroyed. Another type of vaccine is the toxoid vaccine, which uses a toxin made by the disease-causing germ [1].
mRNA vaccines use mRNA, which is a form of RNA that contains genetic material translated by the ribosome to produce proteins. After the protein is created, the mRNA is degraded. The mRNA found in mRNA vaccines is produced in a laboratory and contains a piece of protein found on the virus’s membrane [2]. By introducing the viral mRNA sequence into the body, cells learn how to create the protein on their own. However, once the viral proteins are created, the immune system identifies them as foreign, which stimulates antibody production. These antibodies remain in the immune system, activating when the body is exposed to the disease again. Contrary to the beliefs of some, mRNA COVID-19 vaccines do not cause COVID-19, nor does it affect the body’s DNA [3]. Since mRNA is degraded before it enters the nucleus, which contains the genetic material, genes remain unaffected by the vaccine.
mRNA is extremel
DRAFTJS_BLOCK_KEY:cebm4The first COVID-19 vaccines approved and authorized for use in the United States were messenger RNA (mRNA) vaccines, but what exactly is an mRNA vaccine?
y versatile as a therapeutic agent not limited to vaccines. Applications of mRNA include cancer immunology and protein replacement therapies [4]. However, mRNA is susceptible to degradation by enzymes under physiological conditions, as the body needs to regulate protein translation. Additionally, it is difficult to transport mRNA due to its negative charge, and it needs to reach its target cells to produce specific proteins [4]. Thus, a delivery system that provides efficient and accurate transport and release of mRNA is necessary.
Lipids were introduced as a delivery mechanism in the late 20th century when Robert Malone mixed mRNA with fat droplets. Human cells produced proteins after being coated in this mixture [5]. Soon after, mRNA was delivered to their target cells using liposomes, which are spherical vesicles made of phospholipid bilayers [4]. The core of the liposome can hold both hydrophilic and hydrophobic therapeutic agents, making it a versatile drug delivery apparatus [6]. Later on, lipid nanoparticles (LNPs) were created by binding artificial, positively charged lipids to nucleic acids. The positive charge of LNPs forms a strong bond with the negative mRNA backbone, and the lipids provide stabilization [7].
Despite this discovery, s
cientists have failed to find a suitable lipid for decades. Experiments have shown that positively charged lipids are toxic to animals and humans [7]. Additionally, there was much difficulty in targeting the delivery of LNPs towards specific organs, as they generally accumulated in the liver. The materials needed to produce the LNPs are difficult to source, and this is still a problem when creating the COVID-19 vaccines used today [7].
Today, Pfizer-BioNTech and Moderna’s COVID-19 first and second-dose vaccines are mRNA-based. Meanwhile, the Johnson & Johnson Janssen vaccine is a viral vector vaccine, which delivers an altered version of the COVID-19 virus [8]. The body is then able to produce the protein found on the COVID-19 virus. Although the protein itself is harmless, the immune system is activated by the foreign substance. However, the CDC recommends mRNA vaccines over the viral vector vaccine [8].
With renewed interest in LNP-mRNA vaccines, scientists are pioneering studies using this technology for numerous other diseases. Research is currently examining the formation of a single vaccination that can prevent multiple diseases, which will decrease the number of va
ccines that need to be administered [3]. Since the beginning of mRNA research, scientists have been studying how to use these vaccines for the treatment of various types of cancers, such as pancreatic and colorectal cancers [9]. With mRNA, personalized cancer vaccines can be created to stimulate the immune system to learn how to distinguish cancer cells as foreign and dangerous [9]. More research is currently being conducted to incorporate mRNA into immunotherapy.
Although mRNA technology has existed for a long time, through the COVID-19 vaccines, scientists have been able to harness the versatile mRNA using LNPs. Current research on this topic will surely propel treatment options for a multitude of diseases in the future.
[1] Vaccines [Internet]. National Library of Medicine; [cited 2022 Feb 26]. Available from: https://medlineplus.gov/vaccines.html
[2] What are mRNA vaccines and how do they work?: MedlinePlus Genetics [Internet]. [cited 2022 Feb 26]. Available from: https://medlineplus.gov/genetics/understanding/therapy/mrnavaccines/
[3] Understanding mRNA COVID-19 Vaccines | CDC [Internet]. [cited 2022 Feb 26]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html
[4] Lipid nanoparticles for mRNA delivery | Nature Reviews Materials [Internet]. [cited 2022 Feb 26]. Available from: https://www.nature.com/articles/s41578-021-00358-0
[5] The tangled history of mRNA vaccines [Internet]. [cited 2022 Feb 26]. Available from: https://www.nature.com/articles/d41586-021-02483-w#ref-CR1
[6] Full article: Application of liposomes in medicine and drug delivery [Internet]. [cited 2022 Feb 26]. Available from: https://www.tandfonline.com/doi/full/10.3109/21691401.2014.953633
[7] Without these lipid shells, there would be no mRNA vaccines for COVID-19 [Internet]. [cited 2022 Feb 26]. Available from: https://cen.acs.org/pharmaceuticals/drug-delivery/Without-lipid-shells-mRNA-vaccines/99/i8
[8] CDC. Understanding Viral Vector COVID-19 Vaccines [Internet]. Centers for Disease Control and Prevention. 2021 [cited 2022 Feb 26]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/viralvector.html
[9] How mRNA Vaccines Might Help Treat Cancer - National Cancer Institute [Internet]. [cited 2022 Feb 26]. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer
[Image Citation] Explained: Why RNA vaccines for Covid-19 raced to the front of the pack [Internet]. MIT News | Massachusetts Institute of Technology. [cited 2022 Mar 20]. Available from:https://news.mit.edu/2020/rna-vaccines-explained-covid-19-1211