COVID-19 Vaccines Part 1: How Do They Work?

A changing world

One year ago today we could have never imagined the ways our world would change. A new virus sweeps across the world and grips the headlines almost every day. An already divisive political atmosphere in the United States finds another point of division.

Meanwhile, the convergence of decades of vaccine research combined with over $10 billion in government funding broke down all barriers to achieve the record-breaking development of a brand new vaccine1. The most promising of which uses newly emerging mRNA vaccine technology.

When many Americans hear this, they are skeptical. Concerns abound about being genetically engineered or using a vaccine developed too fast to trust come to many people’s minds. To add to this, a significant amount of Americans have already been skeptical of vaccinations more broadly. This week, let’s address these concerns by looking at how the mRNA vaccines for COVID-19 work.

What’s in it?

The vaccine’s ingredients include mRNA, lipids, salts, and sugar2; all of which are necessary ingredients. We’ll get to what the mRNA does, for now, let’s see what the other ingredients in the Pfizer-BioNTech vaccine do3:

Lipids:

  • 4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)
  • 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (PEG)
  • 1,2-Distearoyl-sn-glycero-3- phosphocholine (DSPC)
  • Cholesterol
A figure showing a lipid nanoparticle (LNP) similar to that used in the mRNA vaccines5.

You don’t need to have a degree in organic chemistry or understand the molecular interactions to understand what these do. In simple terms, they are a mixture of fat molecules which form a microscopic bubble of oil that surrounds the mRNA. This helps the fragile mRNA travel through the body without being degraded by enzymes. It also helps it easily get handed off to cells in your body4.

Salts:

  • potassium chloride
  • monobasic potassium phosphate
  • sodium chloride
  • basic sodium phosphate dihydrate

This is a common mixture of salts called phosphate buffered saline, which helps to keep the pH and saltiness close to that of your body. This same mixture is used in many injected medications. It prevents the vaccine mixture from damaging your cells once injected by matching your body’s conditions. You’ll know why this is important if you’ve ever squirted lemon juice in your eye or heard the expression “rubbing salt on your wounds” to describe something unpleasant.

Sugar:

  • Sucrose

This is simple table sugar which prevents the particles from sticking together when frozen in storage.

Notably, the vaccine contains NO preservatives, eggs, or latex6.

How does it work?

To start, mRNA vaccine technology has never been used to create a widely distributed vaccine. Traditional vaccines for viruses either use a weakened virus or a virus made to be less infectious. These are called attenuated viruses, and once injected expose our body to virus that is unable to cause an infection but which expose our bodies to the virus so we will recognize it the next time around.

The COVID-19 vaccines using mRNA technology on the other hand essentially give our bodies the instructions to make the recognizable feature of the coronavirus. This means our immune system is already on the lookout for it by the time we are exposed to it. This also means that it is impossible to get coronavirus from the vaccine because there is no virus or infectious element in it whatsoever.

A diagram depicting liposome fusion with a cellular lipid membrane delivering RNA7, very similar to the way that vaccine lipid nanoparticles work.

Once injected, the lipid bubbles disperse through muscle tissue and get absorbed by cells as the nanoparticles fuse with their lipid membranes. The mRNA is released into the cytoplasm of the cell, the area of the cell where new parts are built. The mRNA is like an instruction manual for our cells to build a new part: specifically the portion of the spike protein on a coronavirus that triggers our body to be on the lookout for more virus. Once this mRNA is in one of our cells, a protein-building molecule in our cell called a ribosome will construct it in a process called translation; translating mRNA sequence to protein structure made of amino acids.

In the normal cellular process, our cells make mRNA in the nucleus of the cell by copying the sequence from our DNA. This mRNA is then sent away from the nucleus, exiting through a one-way passage out of the double membrane of the nucleus, never to enter again. It is this step that the COVID vaccine skips. It delivers our cells a protein recipe that is not in our DNA and recruits our bodies to essentially make its own vaccine. Notably, mRNA never enters the nucleus, and even if it did, our bodies do not have the ability to use it to alter our DNA8.

A diagram depicting lipid nanoparticle uptake into an endosome, resulting in expression of the spike protein9. Once it is recognized as foreign, a proteasome will destroy it and a piece of it will be displayed on an MHC surface protein.

Once the mRNA is used to create spike protein, it is destroyed by our cell9. The spike protein will make its way to the surface of the cell and be presented to the rest of our body until an immune cell bumps into it. Here are two possible immune cell responses leading to immunity:

If found inside the cell, it will be presented on a protein called MHCI and recognized by immune cells called T cells who will differentiate into Killer T Cells that are on the lookout for anything with the spike protein. These Killer T Cells will bind to any cells who have become coronavirus producing factories, and kill them10.

A figure showing the role of T cells in stimulating antibody or killer T cell responses when encountering an antigen presenting cell (APC)14.

If other immune cells find the spike protein outside a cell, it will engulf it and display a part of it on a surface protein called MHCII, which will bind immune cells called T helper cells, relaying the message to different immune cells called B cells. B cells then differentiate into an immune cell type called a plasma cell, which is an antibody producing factory. In this case it produces antibodies directed against the coronavirus spike protein. If these antibodies encounter the spike protein on an actual coronavirus that enters your body, it will block that spike protein and signal its presence to other immune cells before it gets the chance to infect one of your cells11.

With immune responses like these, we will develop lasting immunity to the coronavirus. Although we do not have enough data to know just how long immunity from the vaccine will last, some experts estimate up to a few years based off of immunity to similar viruses12. Notably, we have not gone over any of the other COVID-19 vaccine technologies such as that being developed by AstraZeneca13. However, the same basic concept is at work: stimulate our cells to make spike proteins so that our bodies already know what to expect.

In part 2, we will explore the major reasons why people hesitate to get the vaccine and try to answer this question: are they safe and effective?

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