mRNA vaccines

An mRNA vaccine is a type of vaccine that uses a piece of genetic material called messenger RNA (mRNA) to instruct the body to trigger an immune response. Previously, many vaccines introduced a weakened or dead piece of a virus or bacterium into the body to jumpstart the immune system. However, mRNA vaccines do not contain any trace of an infectious agent. Instead, they carry genetic instructions that teach the body’s immune cells to make a special protein that mimics an infectious agent. In response, the body’s immune system begins mounting a defense against the targeted virus or bacterium. Scientists had been researching mRNA vaccines for decades before achieving major breakthroughs in the technology in the twenty-first century. That progress proved beneficial in 2020 when several companies used mRNA technology to develop vaccines to combat the COVID-19 pandemic. Widespread vaccination efforts, which had begun in many countries by early 2021 and some of which made use of new mRNA vaccines, were credited with saving millions of lives.

Background

The body’s immune system consists of a series of cells, organs, and tissues that work together to fight off infections. One of the chief weapons used by the immune system are white blood cells, which perform various functions in the fight against invading viruses and bacteria. Macrophages are a type of white blood cell specifically designed to seek out and digest foreign invaders. Macrophages leave behind pieces of the invader known as antigens. The immune system sees these antigens as a threat and begins producing proteins known as antibodies to target those specific antigens.

The body also produces two specialized types of white blood cells called lymphocytes to battle the infection. B-lymphocytes produce antibodies that mark a specific antigen and target it for destruction. T-lymphocytes attack infected cells in the body. One particular type of T-lymphocyte, called a killer T-cell, targets the invader marked by the B-lymphocyte and destroys it. Some lymphocytes can remember a specific antigen and warn the body if the antigen is detected again. This prompts the immune system to produce more antibodies to destroy the invader. In this way, the body can develop immunity to a specific virus or bacteria.

Overview

Vaccines use the immune system’s ability to remember antigens to protect the body against disease. Typically, vaccines introduce a weakened or dead form of a virus or bacterium to prompt the immune system to begin making antibodies. A weakened or dead form of the infectious agent does not cause serious illness, but carries the specific antigen that can be targeted by the white blood cells. As the immune system reacts to the vaccine, it produces lymphocytes that will remember that antigen and respond to the live virus or bacterium if it enters the body.

While these types of vaccines have proven highly effective in fighting disease, they do come with some drawbacks. Chief among these is that a piece of a sometimes-serious biological agent is introduced into the body. Even if the virus or bacteria is weakened, it can still cause some symptoms of the illness. Furthermore, determining how weakened an infection can be and still prove effective is often a long and difficult process.

In the late twentieth century, scientists began to look at a new way to fight disease by using messenger RNA (mRNA). Messenger RNA is a single strand of ribonucleic acid (RNA) that carries instructions from the cell’s DNA. The DNA in the cellular nucleus gives an mRNA strand a copy of instructions on how to make a specific protein. The mRNA travels out into the cell’s cytoplasm, where it transfers that information to complex molecular machines called ribosomes. These ribosomes read the instructions and follow them to make the protein.

Scientists believed that if they could find a way to introduce specially coded mRNA into the body, it could instruct the cells to make specific proteins. These proteins could be targeted to act as disease-fighting antibodies or enzymes that could reverse illness or repair or grow tissue. Researchers began studying the process in the 1960s, and by 1990 had found a way to introduce mRNA into mice. However, using the method on humans proved extremely difficult. The body’s immune system would recognize the laboratory-made mRNA as a foreign invader and destroy it before it could do its job.

In 2005 scientists discovered a way to alter the molecules that made up the mRNA strand to fool the body into accepting it. Soon, they began to view mRNA technology as a potentially revolutionary weapon in the fight against disease. Researchers at several pharmaceutical companies around the world began working with mRNA on potential vaccines for diseases such as cancer, rabies, and influenza. They solved the problem of the immune system attacking the mRNA by further altering its genetic makeup or encasing it in a lipid coating to protect it. A lipid is a fatty acid that does not dissolve in water.

For an mRNA vaccine to work, scientists do not need a sample of an infectious agent such as a virus or bacterium. They only need to know the genetic mRNA sequence the virus or bacteria uses to make its protein coat. When the vaccine enters the body, the mRNA code is consumed by the immune cells. Once inside, the mRNA instructs the cell to begin making its unique protein. The body’s immune system recognizes the protein antigen and begins producing antibodies to destroy it. As a bonus, mRNA vaccines have also been found to trigger the production of killer T-cells, doubling their effectiveness in combatting disease. After the mRNA has done its job, it is broken down and destroyed by the cell.

Researchers had made significant progress on mRNA vaccines by January 2020 when the world faced a global health crisis brought on by the rapid spread of a novel virus. The virus, which came to be known as SARS-CoV-2, caused the disease COVID-19 that infected more than one hundred million people by the end of 2020 and killed more than two million people by that point. Scientists at two pharmaceutical companies—Germany’s BioNTech, which partnered with US company Pfizer, and the US-based Moderna—recognized their mRNA research was well suited to the quick production of a vaccine. Once they received the genetic code of SARS-CoV-2, they were able to create an mRNA strand that mimicked the protein spikes on the virus’s surface. The immune system responded to the protein spikes by producing antibodies to fight COVID-19 without patients ever having to have the virus present in their bodies. By the end of 2020, the companies had produced vaccines that passed through a rapid testing process, were given emergency approval by public health agencies, and had entered distribution in many countries around the world.

Even after the development of these initial COVID-19 vaccines, research into other applications for mRNA vaccines continued. While many companies worked on developing modified vaccines to combat emerging variants of COVID-19, in addition to improvements such as increased potency and reduced side effects as well as doages, other research focused on the potential for mRNA vaccines to combat other viruses, including influenza, the Epstein-Barr virus, and human immunodeficiency virus (HIV). Japan became the first country to approve the use of a self-amplifying mRNA vaccine in 2023.

Bibliography

“COVID-19 Vaccine Basics.” Centers for Disease Control and Prevention, 3 Sept. 2024, www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html. Accessed 9 Dec. 2024.

Fiore, Kristina. “Want to Know More About mRNA Before Your COVID Jab?” MedPage Today, 3 Dec. 2020, www.medpagetoday.com/infectiousdisease/covid19/89998. Accessed 3 Feb. 2021.

Fliesler, Nancy. "Creating the Next Generation of mRNA Vaccines." Harvard Medical School, 29 July 2024, hms.harvard.edu/news/creating-next-generation-mrna-vaccines. Accessed 9 Dec. 2024.

Garde, Damian, and Jonathan Saltzman. “The Story of mRNA: How a Once-Dismissed Idea Became a Leading Technology in the Covid Vaccine Race.” Stat, 10 Nov. 2020, www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/. Accessed 3 Feb. 2021.

“History of Vaccine Development.” World Health Organization, vaccine-safety-training.org/history-of-vaccine-development.html. Accessed 9 Dec. 2024.

Komaroff, Anthony. “Why Are mRNA Vaccines So Exciting?” Harvard Health Publishing, 18 Dec. 2020, www.health.harvard.edu/blog/why-are-mrna-vaccines-so-exciting-2020121021599. Accessed 3 Feb. 2021.

Lowe, Derek. "The First Self-Amplifying mRNA Vaccine." Science, 25 Jan. 2024, www.science.org/content/blog-post/first-self-amplifying-mrna-vaccine. Accessed 9 Dec. 2024.

Pardi, Norbert, et al. “mRNA Vaccines—A New Era in Vaccinology.” Nature Reviews Drug Discovery, vol. 17, 12 Jan. 2018, pp. 261–279, www.nature.com/articles/nrd.2017.243. Accessed 3 Feb. 2021.

“The Power of mRNA” Moderna, www.modernatx.com/en-US/power-of-mrna/science-of-mrna. Accessed 9 Dec. 2024.

Riegelman, Richard. “Population Prevention and COVID-19.” COVID-19 Global Lessons Learned: Interactive Case Studies. Jones & Bartlett Learning, 2021, pp. 31–42.

Tes, Paulida. “Latest Developments in mRNA Technology for Vaccines: Moving Beyond COVID-19.” Pharmacy Times, 2 Mar. 2023, www.pharmacytimes.com/view/latest-developments-in-mrna-technology-for-vaccines-moving-beyond-covid-19. Accessed 24 Apr. 2023.