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How Does the COVID-19 Vaccine Work, and Is It Right for Me?

Amazingly, it has only been just over a year since SARS-CoV-2, the coronavirus that causes COVID-19, entered the United States. The nature and severity of the virus prompted a massive race to create a vaccine, and multiple coronavirus vaccines have been created in less than a year. Given that this process generally takes 5-10 years, this is quite a unique moment in history (1)! While some people are marveling at the speed and multi-national collaboration that went into creating these COVID-19 vaccines, others are concerned about how such a reduced study and trial timeline may have affected their safety and efficacy.

How Does the COVID-19 Vaccine Work, and Is It Right for Me?

How are vaccines developed?

The first part of the vaccine-development process involves research, pre-clinical studies, and submission and approval of an application to the FDA (1). After that, scientists begin three phases of clinical studies and trials, testing for safety and efficacy.

Phase 1 trials are short and have a limited number of volunteers. The purpose is to determine that the vaccine meets certain basic safety standards and to identify the most common reactions to the vaccine (1). Phase 2 trials are larger (hundreds of participants), can last years, and help to determine specifics that will make the vaccine as effective as possible, including the exact makeup, number of doses, and more detailed information on safety and reactions (1).

Phase 3 expands even further to evaluate thousands of participants over several years. Once all three phases are complete and a vaccine is determined to meet specific safety and efficacy standards, the developers submit further applications to the FDA to review and confirm that the vaccine is as safe and effective as clinical studies have stated they are (1).

After applications are approved and public distribution begins, the vaccine enters Phase 4. In Phase 4, the vaccine is closely monitored in order to observe safety and effectiveness as more data comes in, and changes may be recommended to healthcare professionals and the public over time based on this data (1).

How do vaccines work?

Vaccines help the body create immunity to a specific disease without the risk of contracting the disease itself. There are a few different types of vaccines, but each leads to a stimulated immune system that produces antibodies, just like it would if you were infected with the disease itself (2). So, when your immune system encounters the virus in the future, your body can react quickly with the antibodies it learned to produce, and effectively mitigate the threat before it can cause you to get sick from it (2, 4).

So, how was it possible that an effective COVID-19 vaccine could be created in under a year? Both unfortunately and fortunately, the world has experienced outbreaks of coronaviruses in the past 20 years that gave vaccine researchers and developers a head start: they knew of the “spike protein” (3,5). Certain viruses have a specific spike-shaped protein that they use to enter cells, and are easily able to multiply and quickly cause widespread infection (3). Scientists in Oxford, for example, had already developed a vaccine for another coronavirus in 2018 that trained the immune system to target and destroy spike proteins. This means that they had a portion of their initial research for a SARS-CoV-2 coronavirus vaccine completed before the disease that causes coronavirus even existed (3). So, once Oxford scientists gathered enough genetic information about the spike protein of SARS-CoV-2, they were able to modify the existing vaccine to create the Oxford-AstraZeneca COVID-19 vaccine, and achieve efficacy much faster than previously thought possible (3,5).

That is just one type of vaccine - aren’t there multiple? How do they differ?

The Oxford-AstraZeneca COVID-19 vaccine is called a viral vector vaccine (3, 5, 6). It creates the necessary immune response to target the spike proteins by introducing a harmless, non-reproducing virus (in this case, called an adenovirus) into the body that contains DNA with the gene for the protein spikes (7). Once this virus enters a cell, the gene is copied, and the cell actually produces the spikes itself. The immune system activates at this point, alerted by both the adenovirus and the spiked cell, and responds by attacking the spike proteins and creating antibodies (5, 7). Another part of the immune system, called helper T cells, detect spikes when the infected cell dies and can help the body build an even stronger immune response to any future spiked viruses that the body encounters (5).

Another type of vaccine, called mRNA vaccines, include the Moderna and Pfizer-BioNTech vaccines. These vaccines use messenger RNA that cause our cells to make proteins (8). The mRNA is encased in small fatty bubbles to protect it and ensure it can get to cells and enter them (8). It then causes the cell to build spike proteins, and the immune system’s response from this point on achieves the same effect as the Oxford-AstraZeneca vaccine. mRNA vaccines do not contain any part of the virus and cannot cause a COVID-19 infection.

The third class of SARS-CoV-2 vaccine focuses on nanoparticles to create the desired immune response. These nanoparticles, found in vaccines such as the Novavax, are comprised of many protein spikes that have been harvested from infected cells and assembled into many small, multi-spiked nanoparticles (9). These particles cannot cause a COVID-19 infection, but they do prompt the same immune response that can protect from COVID-19 in the future (9).

Which one is the best? How do the safety and efficacy of each vaccine compare with the others?

It is helpful to first define what both safety and efficacy mean in reference to a vaccine. For a vaccine to be considered safe, it must meet certain standards, including remaining below a certain threshold of quantity and severity of adverse effects for a very wide range of people (1). Efficacy means that there is a significant reduction of disease for those who took the vaccine as compared to those who did not (1, 10).

Vaccines that have passed clinical trials and are approved for widespread emergency use in the U.S. are the Moderna and Pfizer-BioNTech vaccines, which means that all are considered safe for the public, even with clinical trial phases being shortened by many years (1, 6, 8, 9). Potential side effects of the SARS-CoV-2 vaccine are similar to that of other vaccines: pain and/or swelling on the arm that received the shot, as well as low-grade fever, chills, headache, or general tiredness for up to three days (1, 11). The Johnson & Johnson, Oxford-AstraZeneca, and Novavax (UK-based) vaccines are both in Phase 3 and not approved for emergency use in the U.S. yet, so they have not been officially determined to be safe for the public at this time, though it is likely that they will be (6).

While there is not much range in terms of the overall safety of the vaccines, the efficacy varies quite widely, due in part to the virus variants that first entered different regions of the world (6):

  • Pfizer-BioNTech: 95%

  • Moderna: 94.1%

  • Oxford-AstraZeneca: 70.4-90%

  • Johnson & Johnson: 72% in the US, 66% in Latin America, and 57% in South Africa

  • Novavax: 89.3% in UK, 49.4% in South Africa

The very high efficacy rates of vaccines such as Moderna have resulted in very low chances of those who receive the vaccine developing even mild COVID-19 symptoms, and a 0% rate of developing severe COVID-19 symptoms (12). While this may change as more people get the vaccine, this is a very promising trend.

What does this mean for you?

It is always worth weighing the pros and cons of each medical procedure or medicine that you choose to take. While the SARS-CoV-2 vaccines that are available now are highly effective and have been shown to be generally safe, there are always exceptions. Current guidelines state that if you have a history of allergic reactions to any ingredient in the vaccine, have had any reaction to the vaccine (even a mild reaction), or are younger than 16, receiving the vaccine is not recommended (13). If you are concerned about the ingredients, you can see the complete list of ingredients for the Moderna vaccine here and the Pfizer-BioNTech vaccine here. It may also be worth considering the timing if you choose to get a vaccine. Allowing yourself a day or two after the vaccine in order to rest and recover if you do develop side effects will help the process.

On the other hand, if you are over the age of 60, have any cardiovascular diseases, or work in a high-risk profession, it may be worth considering the COVID-19 vaccine, even while it is in an emergency-use state. Other factors to consider are if you live in a household with those who are at a higher risk of developing severe COVID-19 or you want to reduce your own risk of developing COVID-19.

Every person has a unique health history and considerations that will play into their decision about receiving this vaccination. We are happy to discuss the optimal choice for you in light of your individual situation. If you would like our input or there are any other factors you are considering about the vaccine that are not addressed in this article, please feel free to reach out to us. We would love to discuss this and any other health concerns or questions you may have. It is our joy to help you and your family make the best decision for your unique situation at each stage of life!


Jonathan Vellinga, M.D.

Jonathan Vellinga, MD is an Internal Medicine practitioner with a broad interest in medicine. He graduated Summa cum laude from Weber State University in Clinical Laboratory Sciences and completed his medical degree from the Medical College of Wisconsin.​

Upon graduation from medical school, he completed his Internal Medicine residency at the University of Michigan. Dr. Vellinga is board-certified with the American Board of Internal Medicine and a member of the Institute for Functional Medicine.




  1. Centers for Disease Control and Prevention. (2020, September 9). U.S. Vaccine Safety - Overview, History, and How It Works. Centers for Disease Control and Prevention.,last%20only%20a%20few%20months.

  2. Centers for Disease Control and Prevention. (2012, March 14). Basics of Vaccines. Centers for Disease Control and Prevention.

  3. Gallagher, J. (2020, November 23). Oxford vaccine: How did they make it so quickly? BBC News.

  4. Why vaccines are critical to keeping diseases at bay. Science. (2020, April 20).

  5. Corum, J., & Zimmer, C. (2020, December 17). How the Oxford-AstraZeneca Vaccine Works. The New York Times.

  6. COVID-19 vaccine tracker. Regulatory Affairs Professionals Society (RAPS).

  7. Centers for Disease Control and Prevention. Understanding Viral Vector COVID-19 Vaccines. Centers for Disease Control and Prevention.

  8. Corum, J., & Zimmer, C. (2020, December 5). How Moderna's Vaccine Works. The New York Times.

  9. Corum, J., & Zimmer, C. (2020, December 30). How the Novavax Vaccine Works. The New York Times.

  10. Centers for Disease Control and Prevention. (2012, May 18). Principles of Epidemiology. Centers for Disease Control and Prevention.

  11. Centers for Disease Control and Prevention. What to Expect after Getting a COVID-19 Vaccine. Centers for Disease Control and Prevention.

  12. Jon Cohen, Sofia Moutinho. (2020, November 30). 'Absolutely remarkable': No one who got Moderna's vaccine in trial developed severe COVID-19. Science.

  13. Centers for Disease Control and Prevention. COVID-19 Vaccines and Allergic Reactions. Centers for Disease Control and Prevention.


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