Quick Guide to the Science of the FDA-Approved COVID-19 Vaccines

 
 Quick Guide to the Science of the FDA-Approved COVID-19 Vaccines

This article provides background information about COVID-19 vaccines that are approved for use in the United States by the U.S. Food and Drug Administration (FDA) and will be updated as new information becomes available. 

As of December 16, 2021, The Centers for Disease Control and Prevention recommends that people choose the Moderna or Pfizer-BioNTech COVID-19 vaccines over the Johnson & Johnson vaccine for both primary vaccination and booster injections due to the risk of rare side effects.

More information can be found in the articles on Phase 3 Clinical Trial Data for the COVID-19 Vaccines.

For information on ages, doses, and booster injections, see the article Who Can Receive the COVID-19 Vaccines and Boosters?

Vaccines are designed to protect us from being infected by pathogens, which are bacteria, viruses, toxins, fungi, parasites, or other microbes. The goal of vaccination is to present the immune system with some part of a pathogen, so that our immune cells will respond and eventually make memory cells. Those memory cells will provide protection if the person is exposed to the actual, active pathogen later in life (see Immunology Basics for more information). 

The trick for making vaccines is to be sure that the vaccine itself does not actually cause illness in the person who is vaccinated. Scientists design a vaccine that is just enough like the active pathogen to prompt the immune system to make protective memory cells without actually causing disease. Over the years, there have been many ideas of how to do this. These different ideas, or approaches, are called vaccine platforms. The different platforms are described in Vaccine Basics. 

Understanding SARS-CoV-2

To understand the specifics of approved COVID-19 vaccines, it is important to understand how active SARS-CoV-2, the virus that causes COVID-19, infects cells. Under a very powerful microscope, an active SARS-CoV-2 virus looks like a ball covered with spikes. These spikes are made of protein. The SARS-CoV-2 virus uses its spike protein to attach to the outside of a healthy human cell. Once attached, the virus is taken inside the cell. It forces the infected cell to make thousands of copies of SARS-CoV-2 viruses. These are then released from the cell to go infect other healthy cells. Therefore, the spike protein is a very important part of the way SARS-CoV-2 infects human cells. If the immune system makes antibodies that stick to the spike protein on active SARS-CoV-2, then the virus can no longer attach to cells and infect them. This is a key strategy for the 3 FDA-approved vaccines: Pfizer-BioNTech, Moderna, and Johnson & Johnson.

The Nuts and Bolts of Approved Messenger RNA Vaccines: Pfizer-BioNTech and Moderna

The platform that the Pfizer-BioNTech and Moderna vaccines use is a messenger RNA platform, which has been under study for at least 15 years. These vaccines do not contain any whole coronavirus or parts of coronavirus; therefore, it is impossible for these vaccines to cause a person to get COVID-19. If the vaccines do not contain any virus or parts of virus, how do they work to cause an immune reaction? Each vaccine contains snippets of genetic information. These bits of genetic information are called messenger RNA (mRNA). The mRNA holds a code which tells cells how to make just one thing – the spike protein from SARS-CoV-2 virus. Because it is fragile, the mRNA is carefully packed into tiny spheres made of lipid (fat) molecules so that the genetic material does not fall apart during transport and injection. The lipid coating is like the colorful shell on the outside of chocolate candies that protects the inside from melting or falling apart. An added benefit of the lipid coating is that it can prompt the innate immune system to react strongly (see Immunology Basics for more information). 

During vaccination, the lipid spheres with the mRNA inside are injected into a person’s arm. Inside the body, the lipid coating helps the spheres attach to healthy human cells. Once attached, the mRNA is taken inside the cells. The cells have a standard mechanism for reading genetic codes and making proteins from the code, because that is how our own genetic code system works. The human cells read the mRNA code for the SARS-CoV-2 spike proteins and then use the code to make spike proteins. The cells then display the spike proteins on their outer surfaces. These spike proteins are not infectious because they are only one part of the virus, not a whole virus. The spike proteins cannot cause COVID-19.

Other immune cells in the area recognize that the spike proteins are “not self” and sound the alarm that a pathogen must have invaded. It is a false alarm—no virus is present—but the immune system does not know that. Immune cells respond rapidly, just as if there were a real infection. The immune system will make many, many antibodies and will eventually make memory cells within weeks of receiving both doses of these vaccines. If a vaccinated person is exposed to active SARS-CoV-2 in the future, the immune system will recognize the spike proteins, and the memory cells will immediately ramp up to defend against infection. 

The Nuts and Bolts of the Approved Viral Vector Vaccine

Unlike the Pfizer-BioNTech and Moderna vaccines that use the mRNA vaccine platform, the Johnson & Johnson vaccine uses a viral vector platform (see Vaccine Basics for more detailed information). To make this type of vaccine, scientists take a common cold virus called an adenovirus. They remove most of the normal adenovirus genetic material. This makes the adenovirus unable to replicate (make copies of itself). It cannot cause an infection. The scientists then place a bit of genetic material from SARS-CoV-2 into the adenovirus. The genetic material, in the form of DNA, holds a code which tells cells how to make the spike protein from SARS-CoV-2 virus. 

The adenovirus holding the spike protein code is injected into the arm as a vaccine. The adenovirus is able to attach to the outside of human cells, and the genetic information is taken inside the cells. Our cells read the genetic code for the SARS-CoV-2 spike proteins and use the code to make spike proteins. The cells then display the spike proteins on their outer surfaces. These spike proteins are not infectious because they are only one part of the virus, not a whole virus. The spike proteins cannot cause COVID-19. 

As mentioned above, other immune cells in the area recognize that the spike proteins are “not self” and sound the alarm. Immune cells respond rapidly, just as if there were a real infection. The immune system will make many, many antibodies and will eventually make memory cells within weeks of receiving one dose of this vaccine. If a vaccinated person is exposed to active SARS-CoV-2 in the future, the immune system will recognize the spike proteins, and the memory cells will immediately ramp up to defend against infection. 

Can Vaccines Cause COVID-19 Disease?

No. Both vaccines may cause some temporary side effects in some people, which in phase 3 trials included sore arm, headache, fever, chills, and body aches. These were usually mild or moderate, lasting 1 to 2 days (see more information in the article on Phase 3 Data). This does not mean the vaccine “caused COVID-19”. When the immune system ramps up and reacts to the spike proteins, the body briefly acts like it has an active infection even though no active infection is happening. That is the cause of the side effects. 

Are the Vaccines Effective Against the Omicron Variant of COVID-19?

In laboratory studies using blood samples from people who have been vaccinated, antibodies from people who received three injections of the Pfizer-BioNTech or Moderna mRNA vaccines were able to neutralize COVID-19 Omicron variant viral particles (prevent them from infecting human cells in a petri dish). The antibodies from people who only received two injections of either vaccine were much less able to neutralize the Omicron variant viral particles. Studies in humans will provide more information about actual effectiveness rates. Based on these laboratory data, The Centers for Disease Control and Prevention recommends that everyone who is eligible get their primary vaccination as well as a booster injection as soon as possible. 

PHASE 3 TRIAL DATA

For more information, we invite you to read our summaries of the phase 3 trial data for each vaccine that led to each vaccine’s FDA approval or Emergency Use Authorization. 

— Jillian Lokere and Aliaa Barakat

References

  1. US FDA News Release. FDA Approves First COVID-19 Vaccine. August 23, 2021.
  2. FDA Briefing Document. Pfizer-BioNTech COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting, December 10, 2020.
  3. FDA Briefing Document. Moderna COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting, December 17, 2020.
  4. PDA Briefing Document. Johnson & Johnson COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting, February 26, 2021.
  5. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020; December 10.
  6. The Centers for Disease Control and Prevention. CDC Endorses ACIP’s Updated COVID-19 Vaccine Recommendations. December 16, 2021.
  7. 5. See I, Lale A, Marquez P, et al. Case Series of Thrombosis with Thrombocytopenia Syndrome following COVID-19 vaccination—United States, December 2020–August 2021. medRxiv. 2021.11.10.21266063
  8. The Centers for Disease Control and Prevention. Omicron Variant: What You Need to Know. 20 December 2