COVID-19 Vaccines: How They Work, Authorization, Side Effects & Ingredients

Following the authorization of COVID-19 vaccines for Emergency Use, conflicting information may influence how the general public feels about receiving the vaccine.

It’s important that individuals and health care providers understand how the vaccine works, the possible risks/benefits, and important facts before deciding to get immunized.

After reviewing the literature, study protocols, FDA briefing documents, and more on the Pfizer-BioNTech and Moderna vaccines, I present my main findings here:

How do These Vaccines Work?

First, let’s quickly review how SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) causes COVID-19:

• SARS-CoV-2 is a positive sense, single stranded, enveloped RNA virus¹
• Spike proteins (S) on the surface of the virus attach to Angiotensin Converting Enzyme 2 (ACE2) host cells and allow for viral entry²
• The virus replicates within the host, may cause mild to severe symptoms, and can spread to other humans

Both the Pfizer-BioNTech and Moderna vaccines have the same mechanism of action using nucleoside modified messenger ribonucleic acid (mRNA) technology:

• The mRNA in the vaccine codes for the spike protein of SARS-CoV-2^1,3
• The goal is to build immunity against the spike protein that the virus uses to infect cells!

1. Lipid nanoparticles (LNPs) are used to encapsulate the mRNA for improved delivery to the cells.^1,3

2. After intramuscular administration, the LNPs enter cells and release the mRNA.

• In the cytoplasm, the mRNA is used to synthesize spike proteins and is then broken down. These spike proteins are expressed on the cell membrane.⁴

3. The body mounts both humoral and cellular immune responses against the spike protein.⁴

• Humoral response creates antibodies specific for the viral spike proteins used to enter ACE2 host cells

• Cellular response involves T cell-mediated activity against the virus

4. If patients are exposed to SARS-CoV-2, their bodies will be equipped with these specific immune cells to fight off the virus.^1,4

Common Myths

You are not injected with the actual Coronavirus:

• The vaccine contains a fragment of RNA that codes for the spike protein only.^1,3

Your DNA will not be affected:

• mRNA is released in the cytoplasm of the cell and does not enter the nucleus (where your DNA is found).⁴

The vaccine trials did not skip safety and/or regulatory steps:

I was surprised when I heard the vaccines would be available so quickly.

During my internship in a pharmaceutical company I learned about how long some clinical trials can take!

So I decided to dig into the history of mRNA technology and the COVID-19 vaccine trials:

• mRNA vaccines have been studied since the 1990s. Some clinical studies have used LNP-encapsulated mRNA to target the Zika virus, influenza virus, and rabies⁴

• The vaccine trials were prioritized by health officials due to the COVID-19 pandemic status. This made the normally lengthy clinical trial processes much faster!

• Both vaccines went through Phase 1, 2, and 3 trials. Studies are ongoing to collect additional safety and efficacy data:
  • BioNTech Phase 1 Start Date: April 23, 2020⁶
  • Moderna Phase 1 Start Date: March 16, 2020⁷

What are the Emergency Use Authorization Details?

The Pfizer-BioNTech vaccine (BNT162b2) was authorized for emergency use on December 11th, 2020.¹

Meanwhile, the Moderna vaccine (mRNA-1273) was authorized for emergency use on December 18th, 2020.³

What Data was Used for Efficacy and Safety Analysis?

The following statistics were used by the FDA to analyze the safety and efficacy of the vaccines.

Pfizer-BioNTech Vaccine (BNT162b2):¹

• Total # of Randomized Participants = 37,796
  • 18,555 received both doses of the vaccine
• 95.0% efficacy: 8 COVID-19 cases in the vaccine group (162 cases in placebo group)

Moderna Vaccine (mRNA-1273):³

• Total # of Randomized Participants = 30,418
  • 13,982 received both doses of the vaccine
• 94.5% efficacy: 5 COVID-19 cases in the vaccine group (90 cases in placebo group)

What are the Common Side Effects of the COVID-19 Vaccines?

Pfizer-BioNTech presented adverse event percentages by age group and dose number.¹

Moderna reported overall adverse event frequencies.³

What are the Ingredients in the Vaccines?

The Moderna and Pfizer-BioNTech vaccines have different formulas. While some ingredients may be hard to pronounce, they fall into 4 simple categories and each serves a purpose:

1. mRNA

Carries the instructions for making the spike protein of SARS-CoV-2.

2. LIPIDS:

Form the lipid nanoparticles (LNPs) that encapsulate the mRNA. This protects the mRNA and improves delivery to the cells.^1,3

• Moderna (4 lipids): SM-102 (proprietary lipid), 1,2-dimyristoyl-rac-glycero3-methoxypolyethylene glycol-2000 [PEG2000-DMG], Cholesterol, and 1,2-distearoyl-snglycero-3-phosphocholine [DSPC])
• Pfizer- BioNTech (4 lipids): 0.43 mg (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg cholesterol

3. SALTS:

These help stabilize the LNPs in solution and serve as pH buffers.

• Moderna (4 salts): Tromethamine, Tromethamine hydrochloride, Acetic acid (found in vinegar), and Sodium acetate
• Pfizer- BioNTech (4 salts): 0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, and 0.07 mg dibasic sodium phosphate dihydrate.

4. SUGAR:

Provides the vaccine with thermal stability.⁵

• Both vaccines contain sucrose.^1,3

*Neither vaccine contains preservatives

I hope this post was helpful. Individuals should always receive thorough information before deciding to accept any medication, vaccine, or therapy.

You can access additional information at the following websites and articles.

REFERENCES

1. U.S. Food and Drug Administration. Pfizer-BioNTech COVID-19 Vaccine (BNT162, PF-07302048). Vaccines and related biological products advisory committee briefing document. 10 December 2020. URL: https://www.fda.gov/media/144246/download
2. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e278.
3. U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee Meeting. FDA Briefing Document: Moderna COVID-19 Vaccine. December 17, 2020. https://www.fda.gov/media/144434/download
4. Maruggi, Giulietta et al. “mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases.” Molecular therapy : the journal of the American Society of Gene Therapy vol. 27,4 (2019): 757-772. doi:10.1016/j.ymthe.2019.01.020
5. Pelliccia, Maria et al. “Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months.” Nature communications vol. 7 13520. 30 Nov. 2016, doi:10.1038/ncomms13520
6. https://clinicaltrials.gov/ct2/show/NCT04380701?term=BNT162-01&draw=2&rank=1
7. https://clinicaltrials.gov/ct2/show/NCT04283461?term=20-0003&draw=2&rank=1