A Recipe for Hope—Part 1: How mRNA Vaccines Work

 

By Caraline Sepich-Poore

 

I was born and raised in Carlsbad and am now in my 5^th year of an MD/PhD double doctorate program at the University of Chicago, training to become both a practicing doctor and an experienced scientist, with the research for my PhD in Biochemistry focused on mRNA. As a medical student, I was offered a COVID vaccine when they first became available. I was looking forward to this because of the decades of research behind them and because of the suffering and death COVID had caused among people I knew. So, like more than 96% of US doctors, I chose to get vaccinated¹. As the vaccines became more widely available, my friends and family asked me many questions about how they worked.

Firstly, what is mRNA? It is a transient molecule used for translating genes from your DNA, or fixed genetic code, into functional parts like proteins. DNA is stored in the core of your cells, or nucleus, protected from damage by two layers of membrane made of fatty, oily molecules called lipids. You can think of your DNA as a master cookbook of all of your family recipes, stored safely in your pantry. Like your cookbook contains many recipes, your DNA contains many genes, each of which encodes how to make something functional — usually a protein. But like your cells and their proteins, you never need to make all the dishes from your giant cookbook at once. So instead, you might get a piece of paper and copy down the instructions for only the dish you want to make. Similarly, your cells make mRNA as a temporary copy of just one gene and transport it out of the nucleus, where it gets translated into protein. Importantly, DNA lasts for the lifetime of the cell (like a hardcover-bound cookbook stored in the pantry), but RNA and proteins don’t last long (like a paper copy and the dish).

So how do the mRNA vaccines work? They use mRNA to encode the spike protein (from the outside of the COVID virus), which trains your immune system to recognize the virus if it enters your body. The mRNA vaccines are made of only a few components: the mRNA encoding the spike protein, a surrounding lipid membrane, and some stabilizers (sugars, salts, etc.)². They don’t contain the virus or the parts needed for it to replicate. Like two drops of oil floating in a pot of water, the lipid particle surrounding the vaccine helps it merge with the lipid membrane of your cells. Then your cells produce the spike protein and present it to your immune system. This is similar to taking a printed recipe of something you found online, making the dish using ingredients from your kitchen, and presenting it to your family for them to try. The printed recipe does not go into your pantry or get integrated into your family’s cookbook, like the mRNA from the vaccine doesn’t enter a cell’s nucleus or mess with its DNA. Furthermore, the printed recipe and dish get thrown away when you’re done, just as the mRNA and spike protein degrade. However, your family still tries the dish and would recognize it if they were served it again. In the case of your immune system, it gets trained to recognize the spike protein as something dangerous. Therefore, the effectiveness (and side-effects) of the vaccine are based largely on your immune response.

An understanding of mRNA and how these vaccines are designed combined with a little scientific history makes it easier to grasp how the mRNA COVID vaccines were made so fast. Studies from the early 1990s first showed that injected mRNA could be used to produce a protein using the cell’s machinery and other studies followed to fine-tune this technology^3,4. The lipid nanoparticle shell was also the product of more than three decades of research, and was already part of another drug approved by the FDA in 2018⁵. After we learned the genetic code of SARS-CoV2, scientists simply had to choose the right mRNA code and stick it into a ready-made capsule.

Based on data in the clinical trials and my personal observations, the vaccines available against COVID are highly effective and safe, reduce the spread of COVID overall, and provide some hope that we now have a tool to reduce the burden of this treacherous virus^6,7.

 

Carlsbad native Caraline Sepich-Poore is a doctoral and medical student at the University of Chicago.

Part 1 of 2: For complete references, please read the article at www.currentargus.com.

A Recipe for Hope — Part 2: Vaccines and the Delta Variant

 

By Caraline Sepich-Poore

 

Now, after vaccines against COVID have been available for months, why do we still have so many cases of COVID? The answer involves the ability of the virus to mutate and the ability of our immune systems to respond (for both the vaccinated and the unvaccinated).

A mutation is a change in a gene that leads to a change in the protein it encodes. For example, if you have a recipe for blueberry pancakes and switch out the blueberries in your written recipe for chocolate chips, you would still be making pancakes, but they would be slightly different, and whoever uses this modified recipe in the future would be making chocolate chip (not blueberry) pancakes. The virus that causes COVID has mutated, creating different variants in the recipe. For example, the delta variant has mutations to the spike protein that make it better at getting into cells⁸. This, in turn, makes it more contagious and dangerous, now affecting younger people more severely⁹.

So how do our immune systems interact with the delta variant, especially after receiving a vaccine? Imagine by getting the vaccine you are training a little army (your immune system) on what the uniforms of an enemy army (the virus) look like. You got the patterns for their uniform and made a part of it to show your cadets what they look like so they will know who to attack when they come around. But the enemy army got a little smart and tricky. They changed their hats. Some armies may have been paying attention to other parts of the uniform and will still recognize the bad guys. Other armies may be more hesitant and confused. Still, others may have either not been paying attention or may have focused mainly on the hats and not recognize the uniforms after the change. How effective the vaccines are against both the original virus or any variant has everything to do with how your immune system responds to the spike protein your cells make after vaccination.

Accordingly, evidence shows that the COVID vaccines usually have high effectiveness and provide good protection, including against the delta variant, because they train your immune system to recognize COVID when you encounter it, though rates of effectiveness are slightly lower against the delta variant than the original alpha variant (88% vs 93.7% for the Pfizer vaccine)¹⁰. Puzzlingly, some vaccinated people can still get “breakthrough infections” of COVID. Usually the symptoms are mild, but can sometimes still be serious¹¹. This has to do with how the patient’s immune response works (or doesn’t work) both in the face of the vaccine and the actual virus. In fact, a recent study shows that tracking the immune response via antibody production after vaccination can be predictive of how well a person is protected from breakthrough infection¹².

Overall, striking evidence worldwide shows that for the majority of people, vaccines do what they were designed to do—protect against severe symptoms that lead to hospitalization and death, in the face of both the original and delta variants^10,11. This is evidenced by data from a few weeks ago from the health departments of 40 states that the vast majority of patients hospitalized with COVID are unvaccinated¹³. In particular, 98% of patients in New Mexico hospitalized with COVID were unvaccinated¹³. Areas with higher vaccination rates also tend to have lower rates of COVID, showing a correlation between vaccination and protection not only on an individual level, but on a community level¹⁴.

Battling COVID at the cellular level is a fight between the virus and our immune systems. If we prepare our immune systems in advance by teaching them what the virus looks like through vaccination, they are more prepared to fight it off, and the virus replicates less. If our immune systems attack more of the virus before it spreads to others, we can protect not only ourselves but our neighbors.

Getting vaccinated is a choice—one that should be made based on facts and in consultation with medical professionals. But it is unavoidable that getting vaccinated is a choice that can benefit you and everyone around you. I chose to get vaccinated not only to protect myself but to protect my family and community.

 

Carlsbad native Caraline Sepich-Poore is a doctoral and medical student at the University of Chicago.

 

Part 2 of 2: For complete references, please read the article at www.currentargus.com.

 

 

 

 

References:

 

1. “AMA Survey Shows Over 96% Of Doctors Fully Vaccinated Against COVID-19”. American Medical Association, 2021, https://www.ama-assn.org/press-center/press-releases/ama-survey-shows-over-96-doctors-fully-vaccinated-against-covid-19.
2. 2021, https://www.uchealth.com/en/media-room/covid-19/a-comprehensive-list-of-all-covid-19-vaccine-ingredients. Accessed 21 Aug 2021.
3. Wolff, Jon A., et al. “Direct gene transfer into mouse muscle in vivo.” Science4949 (1990): 1465-1468.
4. Jirikowski, Gustav F., et al. “Reversal of diabetes insipidus in Brattleboro rats: intrahypothalamic injection of vasopressin mRNA.” Science5047 (1992): 996-998.
5. Cross, Ryan. “Without these lipid shells, there would be no mRNA vaccines for COVID-19.” Chem Eng News(2021): 16-9.
6. Baden, Lindsey R., et al. “Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.” New England Journal of Medicine5 (2021): 403-416.
7. Polack, Fernando P., et al. “Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.” New England Journal of Medicine(2020).
8. Scudellari, Megan. “How the coronavirus infects cells-and why Delta is so dangerous.” Nature7869 (2021): 640-644.
9. “How COVID-19 Delta Variant Is Impacting Younger People”. Https://Newsnetwork.Mayoclinic.Org/, 2021, https://newsnetwork.mayoclinic.org/discussion/how-covid-19-delta-variant-is-impacting-younger-people/.
10. Lopez Bernal, Jamie, et al. “Effectiveness of Covid-19 vaccines against the B. 1.617. 2 (Delta) variant.” New England Journal of Medicine(2021).
11. “What Doctors Wish Patients Knew About Breakthrough COVID Infections”. American Medical Association, 2021, https://www.ama-assn.org/delivering-care/public-health/what-doctors-wish-patients-knew-about-breakthrough-covid-infections.
12. Bergwerk, Moriah, et al. “Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.” New England Journal of Medicine(2021).
13. “See The Data On Breakthrough Covid Hospitalizations And Deaths By State”. Com, 2021, https://www.nytimes.com/interactive/2021/08/10/us/covid-breakthrough-infections-vaccines.html.
14. “Where Are The Newest COVID Hot Spots? Mostly Places With Low Vaccination Rates”. Org, 2021, https://www.npr.org/sections/health-shots/2021/07/09/1014512213/covid-is-surging-in-new-hotspots-driven-by-low-vaccination-rates.