Figure 1: An mRNA Vaccine being prepared
Inactivated vaccines
Consists of viruses, bacteria, or other pathogens that are grown under controlled conditions and killed to reduce infectivity.[1] Viruses are usually killed in a method of heat or formaldehyde while bacteria and fungi are inactivated using a poring method in which the content inside the bacterium is removed and only an intact bacterial cell envelope is left[14]. The pathogens are destroyed so that they cannot replicate or cause disease even in an immunodeficient person but some of their integrity is maintained so they can be recognized by our immune system and elicit an adaptive immune response[2].
The response produced by the immune system is weaker than other types of vaccines and multiple “boosters” may be required sometimes[10]. According to the methods used to inactivate the virus, inactivated vaccines are divided into whole virus vaccine, split virus vaccine, subunit vaccine, which only contains epitopes—the very specific parts of the antigen that antibodies or T cells recognize and bind to, and so on[3]. Examples: Sinovac-Coronavac COVID-19 vaccine, hepatitis A vaccine.
Live-attenuated vaccines
Contains viruses, bacteria, or other pathogens that are harmless and less virulent strain but are still alive and able to duplicate. The principles of passage are applied when producing live-attenuated vaccines. Where the virus or the bacterium is introduced into a foreign host species such as chicken, rabbits, or other tissue cultures [4]. Due to the gene variability and natural genetic mutation, only a small amount of viruses or bacteria can survive and evolve the virulence needed to infect a new host. This strain of virus or bacterium will continue to evolve so that eventually it will lose its virulence to the original host due to lack of selection pressure. This means even if they do not have the ability to infect humans, they can still persist in the body[5].
The live-attenuated vaccine produces an immune response that not only relies on antibodies but also on T cells and macrophages[6]. That’s why the immune response created by it is stronger and lasts longer than the inactivated vaccine, and multiple shots are not necessarily needed. Examples: measle vaccine, yellow fever vaccine.
mRNA vaccines
mRNA is a short-lived, single-strand molecule containing genetic information which is used to produce all types of protein in our body. mRNA vaccines contain mRNA that encodes for the foreign protein of the virus that is delivered to our cells in lipid particles. In the human body, mRNA teaches our body how to make a certain part of a virus or a protein and to identify them as a certain antigen so that adaptive immune response is triggered and our body can produce specific antibodies and prepare for the real virus[7].
mRNA is unstable, fragile, and can easily degrade in cytoplasm since the base pair “U” gives it a relatively short half-life[15]. The delivery improvements include putting mRNA into a lipid nanoparticle, which helps cells to absorb foreign mRNA molecules better[8]. Once the mRNA gets into our body, cells take them up by phagocytosis. After reading the codes on mRNA by internal ribosomes, the cell can produce the protein coded by this specific mRNA. The whole process takes place in the cytoplasm and a few days later, mRNA degrades and never gets into the nucleus so it will never integrate into our own genomes[9].
mRNA Vaccine History:
1989:The first successful transfection of mRNA enveloped in liposomal nanoparticles was reported[9].
1990:It is confirmed by injecting naked mRNA into mice muscle that in vitro transcribed mRNA can produce foreign protein in living tissue[11].
1993:Liposome-encapsulated mRNA is published and shown to stimulate T cells in mice[12].
2000-2008: The first human clinical trial transfecting mRNA that codes for tumor antigen started in 2000 and the results came out in 2008[13].
2020:The Pfizer and Moderna vaccines against COVID-19 came out.
Citations
[1]Petrovsky, Nikolai; Aguilar, Julio César (2004-09-28). "Vaccine adjuvants: Current state and future trends". Immunology and Cell Biology. 82 (5): 488–496. doi:10.1111/j.0818-9641.2004.01272
[2]A. Patricia Wodi, Valerie Morelli. “Epidemiology and Prevention of Vaccine-Preventable Diseases” Chapter 1: Principles of Vaccination
[3]WHO Expert Committee on Biological Standardization (7 January 2016). "Influenza". World Health Organization (WHO)
[4]Jordan, Ingo; Sandig, Volker (2014-04-11). "Matrix and Backstage: Cellular Substrates for Viral Vaccines". Viruses. 6 (4): 1672–1700. doi:10.3390/v6041672
[5]Hanley, Kathryn A. (December 2011). "The double-edged sword: How evolution can make or break a live-attenuated virus vaccine". Evolution. 4 (4): 635–643. doi:10.1007/s12052-011-0365-y
[6]Plotkin, Stanley A., 1932-, Orenstein, Walter A., Offit, Paul A. (Seventh ed.). Philadelphia, PA. 2018. ISBN 978-0-323-39302-7.
[7]Park KS, Sun X, Aikins ME, Moon JJ (December 2020). "Non-viral COVID-19 vaccine delivery systems". Advanced Drug Delivery Reviews. 169: 137–51. doi:10.1016/j.addr.2020.12.008