The bite of the cold stings my cheeks as I scurry, hurriedly, toward the massive steel and glass tower. As I run, I can hear the clacking of my old brown leather shoes on the cold, hard concrete, knowing that each “clack” brings me closer to salvation from the cold. “Clack,” “clack,” “clack,” I’m almost there, walking faster now as my path snakes through the sad garden, devoid of all the life that brings it so much color and vibrancy in the spring and summer. When I finally reach the threshold, the door swings open, I step through and immediately feel the relief of warm air.

Walking by the guards’ station I stop, briefly, to affix the blue, paper mask to my ears, and shuffle past the long line of elderly couples waiting to sacrifice their upper arms for renewed freedom. As I stand there, I think about what an awesome and historic thing it is that I am witnessing. For many of these people, this is their first trip out of the house in months, and yet, I know the only reason it was months instead of years was because the awesome, coordinated effort of the scientific community, the pharmaceutical industry, and the national governments.

A Monumental Achievement

Creating a vaccine is no small task. Before the current COVID-19 vaccine, the quickest a vaccine had made it through development was four years. This vaccine was developed, tested, and produced in a matter of months. This is a feat to be marveled at, and, yes, even questioned. How could a task so immense be completed in so short a time?

There are ultimately a variety of factors that all lined up in the perfect storm to make vaccine development easier and faster. These include financial incentive, the immense global nature of the problem, high levels of community transmission that allowed studies to quickly identify efficacy, policy changes that allowed companies to begin mass production before the end of clinical trials, high levels of interest in study participation, and more. However, the romantic in me says that the most salient reason these arrived so fast is that the immensity of the task in front of us paled in comparison to that of the mighty giant behind us; all we had to do was get on the giant’s shoulders.

You see, a long line of bright individuals came before us, each of them adding their own verse to the Great Play, some developing vaccines, others describing cellular processes, and still others finding ways to employ those processes for the common good. These people, like Franklin, Watson, Crick, Hilleman, and Offitt wrote down everything they did, and, through seemingly endless trial and error, were able to give us a recipe. All we had to do was follow it, and, in fact, long before this new virus was killing millions around the world, we were already using this very recipe and developing the very same technology for use against other diseases, including AIDS, cancer, and ebola.

The Technology Behind the Vaccine

Over the past few months, I have been marveling at this technology and the unique way it’s able to keep us safe. This man-made vaccine actually works very similarly to viruses in nature. Much like viruses, this vaccine also carries instructions for making proteins. These instructions are in an unstable form that never interacts with the longer-term, more stable cellular instructions, the DNA. The instability of these instruction materials and the lack of interaction with DNA are important because they mean that this vaccine disappears entirely from the body within a few hours, leaving behind no permanent changes, except for those physiological immune responses that will protect us.

Unlike whole viruses, the vaccines’ instructions are specific to only one protein, the infamous Spike, and, in some cases, even more specific to only a portion of Spike. Importantly, neither Spike nor our body’s cells have the ability to make more copies of the vaccine’s unstable instructions- another assurance that the vaccine cannot stick around in the body for much longer than a few hours.

Rather than being a protein that has the ability to make copies of viral instructions, Spike can be thought of as the viral key that opens the lock to cells. Without Spike, the virus is unable to enter cells, and it is the goal of these vaccines to ultimately stop Spike from functioning properly.

How does the vaccine go about removing the functionality of this protein when it’s on viruses, though? It aims to do this through the use of one of the body’s most impressive functions- the creation of antibodies. Antibodies are these unbelievable little proteins that attach to and bind up proteins and other particles, but in a highly specific way so that one antibody attaches tightly to only one specific part of a protein and nothing else. If the Spike protein is a key, then an antibody can be thought of as a dummy lock that allows in only that specific key, but once inside, the key can’t be removed, making it useless against the true lock.

Where the Immune System Takes Over

Antibodies are generated through a rather complex process involving a multitude of cell types and cell processes. In the case of the vaccine, this process begins in the muscle cells near the site of injection. Muscle cells (and all cells of the body) constantly produce and degrade proteins. This constant protein turnover maintains the health of the cell and makes sure that it is never using “expired” proteins that may not be functioning correctly.

Because the cells of our body must constantly be creating proteins, there has to be a way to make sure that cells are not creating proteins that differ from what would be expected to come from the body’s overall DNA (differences are often the result of viral instructions, but could also be one of the types of changes to cellular DNA that lead to cancer). One way of doing this involves the immune system. Via this method, the body’s cells cut up small portions of all the proteins they make into little bits and display the pieces on little forks on the outside of the cell. This then allows a type of immune cell, known as a T cell to “taste” the displayed protein bit on the outside of the cell.

It All Starts at T-Cells

Each individual T cell can only “taste” or recognize one piece of protein, and each T cell recognizes something different. So, when the right T cell that can recognize this specific piece of, in this case, Spike, comes into contact with the displayed protein bit, the T cell sends a signal to the muscle cell, telling it to self-destruct. This process is known as apoptosis, one type of cell death. It should be noted that apoptosis, unlike other forms of cell death, is a normal process that happens all the time in the body. Apoptosis does not cause harm or make you weaker, and in fact, without it, we would not have fingers, skin would get thicker as we aged, organs would not stop growing, and cancer would be the rule.

After the cell undergoes apoptosis, two things happen simultaneously. The first is that other immune cells, known as dendritic cells, are attracted to the dead cell and begin to eat the remains. While eating, these dendritic cells chop up small portions of the proteins from the dead cell, and place them on a fork on the outside of the cell, just like the muscle cell was doing. However, this cell’s fork is a little different and it lets T cells know that it’s not directly producing the foreign protein. Rather, this type of fork is designed to act as a sounding board and display to show the protein to as many individual T cells as possible without resulting in the death of the dendritic cell.

Where B-Cells Take Over

The second thing that is going on is that some of the same protein from the dead muscle cell is released freely into the body, and, through anatomical pathways, arrives in the home of the B cells, the lymph node. These B cells have antibodies all over their surface, and each B cell has a slightly different antibody. When the right B cell comes into contact with the Spike protein, it reacts.

Knowing that its only shot against the threat is with numbers, it begins to replicate while also modifying the antibody in each generation to be better and better at both binding to the protein and tagging it for destruction. The B cell needs to make sure the antibody sticks to just that one protein and that, once stuck, it doesn’t fall off. However, the B cell, on its own, doesn’t do this very well. Unless the antibody binding is exceedingly intense or the B cell is able to bind to the protein in multiple locations simultaneously, the B cell needs help from one of the T cells that has recognized the protein shown off by the dendritic cell. It isn’t until these T cells team up with the B cells that robust antibody production can begin.

Every so often some of the new B cells and T cells created in this process branch off and become something different altogether. Some of the B cells become plasma cells while others become memory cells- two cells of extreme importance in response to any vaccine. Plasma cells are B cells that, rather than having antibodies attached to their cell surface, release antibodies into the bloodstream so that they can move throughout the body and appear in virtually every body fluid. These antibodies appear in breast milk, saliva, and blood, so that no matter where the virus may try to enter in the future, it will come into contact with these antibodies and will be unable to enter cells, recognized, and destroyed

Memory B cells are long-lived B cells that stick around in the body for decades. They have the new, improved, and highly specific antibodies developed in the process described above still attached to their surface. Should that protein ever appear in the body again, they will be there to react quickly with their highly effective antibody and lower threshold of activation. Memory T cells are similar, but instead of being a reservoir of effective, easily produced antibodies, they patrol the body looking for displayed protein on those “forks” mentioned earlier.

Once created, these plasma cells and memory B cells form the bulk of the protection we get from vaccines. The antibodies the plasma cells produce, and the surveillance done by the memory B cells prevent infection with anything that produces that same protein. In the case of the two currently approved CoVID-19 vaccines, it prevents infection with SARS-CoV-2 (the virus responsible for CoVID-19) nearly 95% of the time.

An Incredibly Effective Vaccine

95% effectiveness is practically unheard of in other areas of medicine. In obesity medicine, for example, we are often happy when 30% of people lose a clinically significant amount of weight, depending on the intervention, and those interventions usually have to be continued for a lifetime, while this is just two injections. I mean, it just sounds far too good to be true, right? There has to be a catch. In fact, there is- kind of. This vaccine, like all vaccines, and all interventions has some cons. There are two that are important to address here.

Side Effects

The first con is what’s known as vaccine reactogenicity. This is a fancy term for the unpleasant sore arm and sick feeling people often have after receiving a vaccine. Often called a side effect, these symptoms are really the feeling associated with the immune response. So actually, in contrast to a side effect, which is something that we don’t necessarily want to happen in response to a drug, these feelings are the natural consequence of the most important part of getting a vaccine- the immune response and subsequent antibody production. We actually hope to elicit this kind of response, and while not having these symptoms does not mean you do not have protection, the onset of these symptoms can be viewed as a confirmatory sign that the vaccine is working. So, while unpleasant, these symptoms are actually a good sign and only cons insofar as they are uncomfortable for the vaccine recipient.

The next con, and the most worrisome potential complication of the vaccine, is the possibility that the vaccine may cause an allergic reaction. Allergic reactions can sometimes lead to a condition known as anaphylaxis where the immune response to the allergen goes haywire and causes an inability to breathe, extremely low blood pressure, and even death.

However, anaphylaxis follows a well-known sequence of events and can often be effectively treated. So, with proper screening and surveillance before and after the administration of the vaccine, the worst consequences of anaphylaxis can often be avoided. Further, the amount of people who have these reactions to the vaccine is extremely low. For reference, the CDC recently reported that there were 11.1 cases of anaphylaxis per million doses of the vaccine administered, or 1 in 90,090, while a whopping 1 in 2500 to 1 in 5000 cases of anaphylaxis due to penicillin happen each year.

Beyond anaphylaxis and vaccine reactogenicity, there is little about these vaccines that I would call a “con.” The researchers involved in the study looked for as many issues as they could think of in their participants and recorded each one that came up after receipt of the vaccine. No condition appeared in higher amounts in the vaccine group than in the group that did not receive the vaccine with one notable exception.

Severe Reactions?

Bell’s Palsy, a condition characterized by a temporary paralysis of the facial muscles, did occur in four patients that received the Pfizer vaccine, while no one in the group that received placebo developed this issue. However, it is important to note that this is still less than the amount of people we would normally expect to get Bell’s Palsy in the overall population. Bell’s Palsy appears in about 15 to 20 people per 100,000 each year, while, in this trial, only 4 in 30,000 or 13 people per 100,000 developed the issue. So, while this may appear to be a side effect caused by the vaccine, upon further investigation, the vaccine does not increase your chances of experiencing this complication beyond what would normally be expected.

Ok, so far, no other cons have been noticed, but the trials were so short. Couldn’t there be more of these cons later on that we just haven’t noticed yet? Technically, yes, that is a possibility. You can never truly know anything until you test it, and this virus hasn’t been around very long.

However, this vaccine is removed from our bodies extremely quickly. As discussed above, it has no ability to make more of itself in the cell, it does not get near our DNA, and its half-life (the amount of time it takes for half of the vaccine to be degraded) is exceptionally short. So short, in fact, that these vaccines must be kept extremely cold in storage to keep them from expiring.

The only lasting effect this vaccine is known to have is antibody production, and there has been no confirmed case, to my knowledge, of an antibody causing issues years after its production. These two things combined make it very unlikely that these new vaccines will cause any untoward issues years after their administration.

Further, while it is possible that as more and more people receive this vaccine, we could begin to detect some extremely rare issues that may not have occurred in the 30,000 people sampled in the study, these would have to be extremely rare and very unlikely to affect any one person.

The Big Picture

That said, CoVID-19 has already infected an estimated 1/3 of the United States, with a death rate in those 60 and older of one in 58 people infected and 1 in 10,000 in those younger than 40. Any side effect not yet uncovered by the trial would be expected to occur in fewer than 1 in every 30,000 people (the number of people enrolled in the trial) and it would be expected to result in death in even fewer people than that. The potential danger posed by these as yet undetected adverse effects appears to pale in comparison to the known dangers of CoVID-19.

These vaccines are a marvel of the modern world. In the moment we most needed them, scientists, businesses, and governments were all able to come together to produce an absurdly effective, highly safe solution to our mutual problem. Despite that, they are not perfect, and, often, getting them is not fun. However, if we do not make use of them, the efforts of all these great men and women will be for naught.

Turning, hurriedly, up the stairs now with my blue mask properly affixed to my face, I reflect on the patriotic nature of getting the vaccine. It occurs to me that if enough people don’t get the vaccine, others who cannot get the vaccine will continue to be forced to live without freedom and in fear of the virus, and others will continue to die in harrowing numbers. We, as Americans, have a duty to defend these peoples’ lives and freedom from the attacks of this virus. We have a duty to bare our arms.