As always, we’re geeked to have Raymond write another piece for us. But this time around, he’s not just a cultured, bright young man with an opinion. In fact, he’s writing as a final-year student pharmacist exploring today’s most pressing discussion: COVID-19 vaccinations.
How do vaccines really work? What makes these new COVID-19 vaccines so groundbreaking? Should we be skeptical? For the good of the culture, University of Minnesota-Duluth PharmD candidate Raymond Kindva will answer those questions and more.
DISCLAIMER: I’m no expert on vaccines and the information presented here is based on my own research on the topic. Please consult vaccine experts and/or visit the CDC, FDA, Pfizer, and Moderna’s official websites for more information.
But before I get all nerdy about these vaccines, let’s do a brief background on vaccines and explore what makes the COVID-19 mRNA vaccine a medical technological marvel.
With reports of positive results from recent studies on Pfizer and Moderna-sponsored COVID-19 vaccines, a vaccine is finally available. On December 10, 2020, the FDA’s vaccine advisory committee held a public hearing about Pfizer’s vaccine and recommended emergency use approval to be granted by the FDA. As of the next day, the FDA granted emergency use approval for use of Pfizer’s vaccine which means vaccinations against COVID-19 will soon be a reality.
What is the big deal with vaccines anyway?
The human body is equipped with a powerful weapon called the immune system. The immune system consists of different specialized cells that carry out a variety of functions like recruiting other immune cells, eliminating infectious agents, destroying infected cells, creating “memory” cells, releasing antibodies, and sending signals to other body functions.
The immune system fights anything in your body it deems foreign or harmful, sending alert signals—such as fevers or allergic reactions—and, in patients with autoimmune conditions, sometimes even attacking the body itself. In fact, the immune system can trigger a complete shutdown of the body’s organs if it thinks it’s losing against the infection. To prevent such a scenario from occurring, the immune system develops a “memory” where it remembers the infection and trains the body to effectively fight it in case of re-infection.
This is where vaccines come in.
Vaccines basically trick your immune system into thinking it is under attack. The goal is for the body to recruit the immune cells and train them into recognizing signs of infection without alarming the entire body. This prepares the immune cells to correctly identify infectious agents, recruit specialized cells, and attack infectious agents that enter the body guided by stored “memories” of the previous attack.
It should be noted that there are different types of vaccines:
- Weakened (attenuated) live vaccines – vaccines containing the live infectious agent(s). The live agent is weakened enough for the immune system to recognize and attack it without alarming the body.
- The live agent can still infect cells and multiply, but this does not cause severe sickness. The danger, though, is that the live agent can take advantage of a body with a weakened immune system, so it is not recommended for immunocompromised persons such as patients with HIV, organ transplants, or undergoing chemotherapy.
- Examples of this type of vaccine: MMR (measles, mumps, and rubella), varicella
- Inactivated vaccines – vaccines with infectious agents that have been killed. It removes the risk of infection since dead agents cannot multiply or infect cells. The immune system can still recognize, defend, and create a “memory” of the agent(s) for possible future attacks.
- One dose is usually not enough for the immune system to develop a strong and lasting immune response. Several doses of these vaccines are often needed to maintain long-term immunity.
- Examples of this type of vaccine: flu (given as a shot in the arm), polio
- Subunit, polysaccharide, toxoid, and conjugate vaccines – vaccines with fancy terms meaning they use a part or parts of the infectious agent which the immune system recognizes as harmful. These vaccines are easier to make since only the parts that the immune system recognizes are needed. On the other hand, the vaccine still requires multiple doses to be effective.
- Examples of this type of vaccine: shingles, pneumococcal
Alright, so what’s special about this mRNA vaccine?
mRNA or messenger RNA is a molecule found in every living cell that acts as a template for making proteins. Proteins are not unique to humans and are found in nearly every living organism including viruses. In fact, SARS-COV-2, the virus that causes COVID-19, has unique spike proteins that allow it to attach to human cells and infect them. With this knowledge, recent genetic technology has been used by researchers to sequence the SARS-COV-2 genetic code. Why? To develop mRNA templates that can encode the SARS-COV-2 spike protein.
If the body’s cells can read the mRNA encoding information for the production of the SARS-COV-2 spike protein, creation of the protein by body cells can become a trigger for the body’s immune system in place of a dead or weakened version of the actual virus.
It is challenging and expensive to create a vaccine with live or dead viruses, but the use of genetic technologies has allowed for fast and cheap replication of mRNA encoding the SARS-COV-2 spike protein to be delivered to human cells via encapsulated lipid nanoparticles (LNPs)—here’s info on that if you want to keep digging.
Basically, LNPs help “sneak” the vaccine (mRNA with spike protein information) into human cells. The mRNA then tells the body’s cells to create the spike protein, allowing the immune system to identify SARS-COV-2 without having the actual virus injected into the body. Such technology is also being used to create mRNA vaccines against certain cancer types.
So what is the evidence for Moderna and Pfizer mRNA vaccines’ effectiveness?
On December 10, 2020, Pfizer published interim results (summary on page 32) of their mRNA vaccines trial which enrolled 30,000 people from Argentina, Brazil, South Africa, and the United States.
Currently, Pfizer’s BNT162b2 vaccine will be administered as a 2-dose vaccine given 3 weeks apart while in clinical studies, Moderna’s mRNA-1273 vaccine was given as two intramuscular doses four weeks apart.
For vaccines to be considered effective by FDA standards, they must achieve at least 50 percent efficacy benchmark in all patients that enrolled compared to placebo in addition to safety requirements.
Interim results from the Moderna trial found a 94.1 percent effectiveness in COVID-19 prevention after 14 days of the last vaccine dose; based on 196 cases analyzed, 11 patients develop COVID-19 compared to 185 in those who received the placebo. The Pfizer trial found a 95 percent effectiveness in COVID-19 prevention after 7 days of the last vaccine dose; based on 170 cases analyzed, 8 patients develop COVID-19 compared to 162 in the placebo group.
There is still a lot of data from both studies that haven’t been reported yet, and clinical trials always have nuances based on their designs and the populations studied. There are also logistic challenges of producing and distributing millions of COVID-19 vaccines in a global scale. Both vaccines are to be frozen for transport making effective distribution difficult and expensive.
Additionally, there are several questions yet to be answered: will the vaccines be annual like the flu vaccine? Will additional booster vaccines be needed? Will it work in special populations such as pregnant women, children, and immunocompromised patients? What are the long-term effects of the vaccine? These are really important questions that will be answered only once a full report of completed clinical studies are published and peer-reviewed.
Also, the trials do not prove whether the vaccines are capable of stopping transmission of COVID-19 in those who receive it. They only show that the vaccines can prevent symptomatic COVID-19 infection. Do not expect quarantine to be over just yet since majority of transmission is done by asymptomatic individuals.
Wait, there have to be side-effects, right?
Of course, any substance that enters the body comes with the risk of side effects.
Side-effects observed in the Moderna vaccine trial were fatigue and headache while fatigue, muscle/joint pain, and headache were observed in the Pfizer trial. These side-effects often occurred the first few days after receiving the vaccines and are considered “mild” which means they were short-lived and don’t require hospitalization.
However, it is important to note that most pharmaceutical products such as vaccines go through three different clinical trial phases to ensure safety. Phase 1 trials generally enroll the least number of subjects to study the safety profile of the product. Only after passing phase 1 trials are phase 2 trials performed to evaluate the efficacy and safety of the products in a larger sample population. Successful completion of phase 2 trials may lead to accelerated FDA approval of the product depending on the quality of evidence, but phase 3 trial results are usually used by the FDA to grant approval.
Vaccines, in particular, require phase 3 trials to compare their efficacy and safety to “standard-of-care”—basically current treatment for COVID-19. This is to determine superiority or non-inferiority of the vaccine efficacy and safety and has the largest enrollment of the patients compared to phase 1 and 2 trials.
So far so good, but do I really need this vaccine?
Honestly, it is ok to have a healthy dose of skepticism about the results of the Moderna and Pfizer vaccines, especially since there is still data being collected from the clinical trials that hasn’t been reported yet. However, the results are extraordinary in terms of the percentage of patients who had immunity against COVID-19 when given two doses of either vaccine. For this reason, it is advisable to get the vaccine as soon as it becomes available to you.
Also, given the constraints of manufacturing and transporting millions of the vaccine doses, the first batches will be limited to persons at high-risk of getting COVID-19 infected such as healthcare/nursing home workers. It is also likely that the vaccine will be provided for no cost to the population, but that’s still an uncertainty.
There is a lot out there about mRNA vaccines and COVID-19 vaccines, but I hope I was able to provide useful info about them and effectively explain the science behind vaccines. For further info, check out the following podcasts: WNYC’s Radiolab episode on The Great Vaccinator, On The Media’s A Dose of Reality episode, and NPR’s 1A Explaining The Science Behind An mRNA Vaccine For COVID-19. For visuals, check out this YouTube video brief summary on mRNA vaccines.