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mRNA Vaccines: The Next Generation Tool to Fight Infections

VME-34
Veterinary Preventive Medicine
Date: 
08/24/2021
Scott P. Kenney, PhD, Assistant Professor, Ohio Agricultural Research and Development Center, The Ohio State University Vaccines

Vaccines have been used by humans for over 225 years to prevent serious illness or death from infectious agents. Immunization currently prevents 4–5 million deaths every year (World Health Organization 2021). Vaccination allows the body to educate your immune system to recognize and eliminate foreign invaders (pathogens) before they cause disease. Several vaccines, such as those for smallpox in humans and rinderpest in cattle, have been so successful the disease is all but gone (Greenwood 2014).

Traditional Vaccines

Traditional vaccines can be divided into three types:

  • inactivated
  • live-attenuated
  • subunit 

Inactivated vaccines treat:

  • the flu (shot)
  • hepatitis A
  • polio (shot)
  • rabies

Inactivated vaccines are made by growing the pathogen in a controlled laboratory setting and killing it in a manner that makes it incapable of causing disease.  

Live-attenuated vaccines treat:

  • measles/mumps/rubella (MMR)

  • rotavirus

  • smallpox

  • chickenpox

For this type of vaccine, the pathogen is grown repeatedly in artificial conditions that damage its ability to cause illness in its natural host. These defective pathogens can then be given to healthy people whose immune systems fight off the weakened virus without causing any disease.

Subunit vaccines use a small, artificially-created piece of the pathogen. They use this piece or in some cases link it to another attenuated pathogen that allows the fragment to induce a better immune response. As only pieces of the pathogen are used, there is no chance for illness from this kind of vaccine (Pollard and Bijker 2021).

Emerging Vaccines

Scientists and medical professionals are constantly working to improve their ability to make vaccines faster, cheaper, more effective against newly emerging diseases, and more effective against the authentic pathogen. As technology has improved, the options for creating vaccines has expanded greatly. mRNA vaccines are the result of technological advances that allow scientists to make effective vaccines very quickly to treat new unknown pathogens. The COVID-19 vaccines designed by PfizerBioNTech and Moderna contain lipid (fat) entrapped mRNA that is encoded with the spike protein from SARS-CoV-2, the causative agent of COVID-19 (Meo et al. 2021).

mRNA 

Graphics showing the progression of DNA to RNA to Protein to Cells to Organs to a complete Organism, like a human.

Figure 1. DNA and RNA are the building blocks of life. Graphic: by Scott P. Kenney, The Ohio State University

All life is composed of DNA, RNA, and proteins, among other substances (Witkowski 2005). DNA stores your genetic information and tells the cells of your body how to function properly. DNA has multiple genes, and it sends the protein synthesis messages of each gene through messenger RNA (mRNA). These protein synthesis messages are then used to produce proteins. The proteins, along with other biomolecules, assemble into cells. The cells group into tissue and the tissue creates organs. This process continues until your entire body is built (Figure 1). Scientists can now create DNA and RNA outside of a cell and include genetic messaging that is useful for: 

  • replacing proteins that are missing in some sick people.
  • creating vaccines. 

     

mRNA Vaccine

Typically, mRNA in your body is quickly made into protein. The RNA then breaks down while the protein sticks around to carry out additional functions. RNA breaks down because it is vulnerable to enzymes called RNases (Gupta et al. 2013) and has a hard time getting into cells from outside. If foreign RNA gets inside cells, the proteins it produces trigger an immune response that quickly removes the RNA from the cells (Hartmann 2017). But new technology is allowing mRNA to be made outside of the cell and then returned to the cell to make protein based on the new RNA’s protein synthesis instructions. This new mRNA is designed to last a little longer than normal and look more like natural mRNA to prevent it from being broken down or recognized by the immune system (O'Donoghue and Heinemann 2019). Further, the mRNA is protected by being encased in nanomaterials such as lipids, which helps it to get into cells (Reichmuth et al. 2016). This new mRNA makes viral proteins that get recognized by the immune system, which results in an immunity response that destroys the proteins.

Food and Drug Administration (FDA) Approval Process

Any new technology used on humans undergoes rigorous testing to ensure it is safe and effective before it is given to large numbers of people. The FDA regulates the approval of new technology in the United States (Darrow, Avorn, and Kesselheim 2020) following a basic process: 

Research and development – Scientists in the lab test whether their ideas for a vaccine work in laboratory or animal experiments.

Preclinical testing – Additional laboratory research and testing is conducted using animals to determine how the vaccine works and if it is likely to be safe and work well in humans.

Investigational New Drug Application – An application is filed with the FDA and scientists carefully study the preclinical data to ensure safety and efficacy.

Phase I clinical trial – Twenty to 100 volunteers are given the vaccine to focus on safety and whether any adverse reactions occur.

Phase 2 clinical trial – Various dosages are tested using randomized-controlled studies (some people get the vaccine, and some don’t) on hundreds of people with different health statuses from various demographic groups.

Phase 3 clinical trial – Thousands of people are vaccinated. Studies review the effectiveness while further evaluations are conducted on safety. 

FDA approval – Upon completion of testing that shows the vaccine or drug is safe and effective, the product gains FDA approval for use in a specific treatment.

Different Types of mRNA Vaccines Yet to Come

Since mRNA vaccines have been shown to be safe and effective against COVID-19, we can expect to see more vaccines utilizing this technology in future human and animal vaccines. Further study on the longevity of the immune response from these vaccines will be critical to improving their usage and efficacy. Each new mRNA vaccine will go through the strict process of FDA approval before being released for public use.

Questions?

Concern about new technologies and vaccination in general is natural. Overcoming these concerns and being vaccinated, if eligible, is critical to stopping the spread of certain diseases and preventing serious illness. If you have vaccine doubts, the best course of action is to talk with your primary care physician. Doctors can discuss which vaccinations you should have and provide sound medical advice on any concerns. If you have further questions, you can contact the Centers for Disease Control and Prevention (CDC) information number at 800-CDC-INFO or 800-232-4636. 

Graphics showing how mRNA vaccines enter cells, which makes antigens, which the immune system makes antibodies against, which kill the virus..

References

Darrow, Jonathan, Jerry Avorn, and Aaron Kesselheim. 2020. "FDA Approval and Regulation of Pharmaceuticals, 1983-2018." JAMA, 323 (2): 164–176.

Greenwood, Brian. 2014. "The contribution of vaccination to global health: past, present and future." Philosophical Transactions of the Royal Society B, Biological Sciences. 369, (1645):
doi.org/10.1098/rstb.2013.0433

Gupta, Sandeep, Brendan Haigh, Frank Griffin, and Thomas Wheeler. 2013.  "The mammalian secreted RNases: mechanisms of action in host defence." Innate Immunity, 19 (1): 86–97.

Hartmann, Gunther. 2017. "Nucleic Acid Immunity." Advances in Immunology, 133: 121–169.

Meo, Sultan, Ishfaz Bukhari, Javed Akram, and David Klonoff. 2021. "COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines." European Review for Medical and Pharmacological Sciences,  25, (3): 1663–69.

O'Donoghue, Patrick, and Ilka Heinemann. 2019. "Synthetic DNA and RNA Programming." Genes (Basel), 10 (7): 523.

Pollard, Andrew, and Else Bijker. 2021. "A guide to vaccinology: from basic principles to new developments." Nature Reviews Immunology, 21, 83–100.

Reichmuth, Andrew, Mattias Oberli, Ana Jaklenec, Robert Langer, and Daniel Blankschtein. 2016. "mRNA vaccine delivery using lipid nanoparticles." Therapeutic Delivery, 7 (5): 319–34.

Witkowski, Jan. 2005. The Inside Story: DNA to RNA to Protein. New York: Cold Spring Harbor Laboratory Press.

World Health Organization. 2021. "Immunization coverage." Key facts. July 15, 2021.
who.int/en/news-room/fact-sheets/detail/immunization-coverage

Topics: 
Originally posted Aug 24, 2021.
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