The Pfizer vaccine (BNT162b2) and Moderna’s (mRNA-1273) are based on mRNA (m means messenger). To understand this vaccine well, we have to know the RNA well. For this, a quick refresh of the central dogma of molecular biology:
DNA, which consists of combinations of four nucleotides, represented by the letters A, G, C, and T, contains the information to produce all the proteins in an organism. The DNA in your cells replicates by making one copy each time a cell divides into two. All the information compiled in the DNA of an organism makes its genome, which is like a library of genes. Each gene has the information to synthesize a protein. It happens that this information stored at the DNA, which is in the nucleus of the cell in double-strand form, passes first to single-stranded mRNA (m from messenger) of nucleotides represented by A, G, C, and U (in RNA, there is U instead of T). The mRNA leaves the nucleus of the cell to carry the information to the cellular cytoplasm, where the ribosomes, which are protein factories, translate such information to synthesize proteins.
Football/Soccer can also help to remember that the mRNA acts as a messenger of information so that something is executed. In the 2008 Eurocup final, in Vienna, Marcos Senna DNA had the ball in the central circle, Xavi Hernández RNA acted as a messenger receiving and passing the ball to the edge of the area so that Protein Torres could do his job scoring the goal of the victory of Spain against Germany.
Once you understand the concepts of DNA, RNA, and protein, I can tell you that all the existing vaccines, and those that are being developed, against COVID-19 seek, in different ways, to deliver a specific protein of the SARS-Cov-2 virus, the Spike protein (or protein S) inside human cells3. The Spike Protein is the most characteristic and particular protein of the virus, and that is why it is used to give the false call to our immune system that the virus is in our cells. One inside our cells, Spike Proteins cannot replicate by themselves or cause damage, but our immune system is capable of detecting them. Set Spike Protein into human cells can be achieved by introducing DNA (in benign viruses called adenoviruses), as in the case of the AstraZeneca / Oxford, Johnson & Johnson, and Russian Sputnik V vaccines, or by introducing RNA messenger, such as it happens using Pfizer or Moderna vaccines. With this information, our cells will use their own machinery to produce the Spike Protein of the SARS-Cov-2 virus.
Some other vaccines in development, such as Sanofi or Novavax, plan to introduce fragments of the Spike Protein.
You have to know the vaccines ready to jump into the pitch to have confidence in them. Let’s focus on those based on RNA. I understand that if you hear that they will inject Ribonucleic Acid (RNA) modified with pseudouridines in your body, the first thing that comes to mind is: «You go first. I’m not in a hurry.» But you shouldn’t be scared. Messenger RNA is a very fragile molecule that breaks down quickly. That is why they have to protect it with modifications to last a little while in the cell until it synthesizes a few proteins. Introducing RNA into the cell without these modifications would be like Messi playing without shin guards; he would soon leave the field injured. The RNA molecules in vaccines have shin guards placed on the sides in the form of UTRs (from UnTranslated Regions, which are nucleotides that are not recognized by the protein-making machinery)4. Besides, at the front end, they wear a cap made of a modified nucleotide that protects them from the degradation of RNA-eating enzymes and, at the posterior part, they have a protective tail that also helps the RNA to be translated into protein. Finally, the RNA of the vaccine instead of uracil nucleotides carries pseudouridines that camouflage the modified mRNA from immune reactions of our body to unknown RNAs.
Therefore, the RNA used in the vaccine enters the cell as Messi playing with American Football protections. Finally, the RNA in these vaccines is wrapped in a lipid nanoparticle, something like a microdroplet of oil, and is accompanied by some salts and sucrose5. It could give some small side effects as other vaccines or drugs, but there is no scientific or medical reason why this vaccine should worry you.
I understand that some other type of vaccines could raise some concerns, such as vaccines that use attenuated viruses 6. Imagine that SARS-Cov-2 is manipulated in the laboratory to minimize its ability to replicate, and that weakened virus is used to make a vaccine. This strategy of using attenuated viruses has served in some cases, such as to eradicate Polio disease. But don’t worry, none of the vaccines approved for COVID-19, or in the process of approval, use attenuated viruses.
Again, all COVID-19 vaccines only seek to introduce the Spike Protein of the virus into your cells. When you are vaccinated with the Pfizer or Moderna vaccines, you will get a temporary RNA, which will produce a few Spike Proteins before disappearing. That RNA cannot replicate nor to insert itself into your DNA because, on the one hand, it does not mix (recombine would be the term) well with your DNA, and on the other, it does not enter the cell nucleus (where the DNA is) to perform its function.
The RNA vaccines would be as having Guardiola or Mourinho as coaches for a short period of time, just enough for them to teach in your youth academy, which is your immune system. In a few weeks, you will continue to have your DNA intact, but with the messages received by Guardiola or Mourinho you will be almost unbeatable (95% probability of not being infected, as I will mention below) against the COVID-19 virus. These elite coaches may have to come back later, in one, three, or ten years, but we already have their phone number and their availability to contract them when necessary.
RNA vaccines are novel vaccines, but they have been investigated for a few years already and have been tested for other diseases such as cancer in Phases I and II of clinical trials7. They will instruct your cells to produce the Spike Protein of the SARS-Cov-2 virus thus tricking your immune system into reacting as if it had to defend itself from the complete virus, through the innate immune system (T lymphocytes) or the creation of antibodies (by B lymphocytes)8. The immune system will remember and thus will recognize and inactivate everything that has a Spike Protein, such as the SARS-Cov-2 virus. You will make a very elegant dribble to the immune system, at the level of Romario cow’s tail.
- Krammer, F. SARS-CoV-2 vaccines in development. Nature 586, 516–527 (2020). https://doi.org/10.1038/s41586-020-2798-3. https://www.nature.com/articles/s41586-020-2798-3
- Jackson, N.A.C., Kester, K.E., Casimiro, D. et al. The promise of mRNA vaccines: a biotech and industrial perspective. npj Vaccines 5, 11 (2020). https://doi.org/10.1038/s41541-020-0159-8 https://www.nature.com/articles/s41541-020-0159-8
- Pfizer/Biontech COVID-19 vaccine Fact Sheet
- Pollard, A.J., Bijker, E.M. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-020-00479-7
- Pardi, N., Hogan, M., Porter, F. et al. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov 17, 261–279 (2018). https://doi.org/10.1038/nrd.2017.243
- Pardi, N., Weissman, D. Development of vaccines and antivirals for combating viral pandemics. Nat Biomed Eng 4, 1128–1133 (2020). https://doi.org/10.1038/s41551-020-00658-w