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A quick guide to how different COVID-19 vaccines work

Learn how different types of vaccines prepare your immune system for an encounter with the coronavirus.

A pharmacist administers a COVID-19 vaccine into the upper arm of a male patient.

Updated on June 6, 2025

COVID-19 is a respiratory illness caused by the SARS-CoV-2 virus, a virus that was first discovered in late 2019 and was declared a global pandemic in March 2020. Since May 2023, COVID-19 is no longer considered a public health emergency, though it remains a persistent public health concern.

Vaccines that provide immunity against COVID-19 played an important role in resolving the public health emergency caused by the SARS-CoV-2 virus, and vaccines continue to play an important role in protecting people against severe illness caused by the virus and reducing the spread of the virus.

Currently, there are three COVID-19 vaccines used in the United States. Two of these vaccines are mRNA vaccines. The third vaccine is what is called a protein adjuvant vaccine. These terms refer to the different mechanisms that the vaccines utilize in order to create immunity against COVID-19 infections. All three are considered safe and effective options.

Here is a closer look at how mRNA and protein adjuvant vaccines work.

mRNA vaccine

Both the Pfizer and Moderna vaccines are messenger RNA (mRNA) vaccines. This type of vaccine has been studied for over half a century, though the Pfizer and Moderna vaccines are the first mRNA vaccines to be approved and to see widespread use by the public.

Both mRNA vaccines are delivered with intramuscular injections, typically into the upper arm. These vaccines contain mRNA, a genetic substance that contains instructions for making proteins. Specifically, the mRNA vaccines contain instructions for making the S protein, or “spike protein,” found on the surface of the SARS-CoV-2 virus. This spike protein protrudes from the surface of the SARS-CoV-2 virus to help it attach to a cell inside the body.

When introduced into the body, mRNA vaccines cause cells to produce this spike protein. As these proteins move through the body, the immune system will make antibodies (infection fighting immune proteins) capable of fighting off the virus that causes COVID-19.

RNA is not the same as DNA, and none of the COVID-19 viruses interact with or change a person’s DNA.

Protein subunit

The COVID-19 vaccine from the manufacturer Novavax is a protein subunit vaccine. It contains a version of the S protein or “spike protein.” Spike proteins on their own are harmless and do not cause infection. The vaccine does not contain an actual virus. Introducing spike proteins into the body with a vaccine will cause the body to produce antibodies that will attach to the virus that causes COVID-19.

This vaccine also contains an adjuvant, an ingredient that helps create a stronger immune response.

Choosing a vaccine

All three vaccines are considered safe and effective and are approved by the U.S. Food & Drug Administration. All three have been updated to protect against newer strains of the virus that causes COVID-19. All three have been shown to reduce the risk of severe infection and hospitalization from COVID-19 infections.

Recommendations for vaccines vary depending on a person’s age, health, risk of severe COVID-19, and medical history (such as adverse reactions to other vaccines). Your best source of information will be a healthcare provider or a pharmacist.

Article sources open article sources

Centers for Disease Control and Prevention. About COVID-19.
David J. Sencer CDC Museum: In Association with the Smithsonian Institution. CDC Museum COVID-19 Timeline.
United Nations. WHO chief declares end to COVID-19 as a global health emergency.
Centers for Disease Control and Prevention. Overview of COVID-19 Vaccines and Vaccination.
Kathy Katella. Comparing the COVID-19 Vaccines: How Are They Different? Yale Medicine.
Johns Hopkins Bloomberg School of Public Health. The Long History of mRNA Vaccines.
Mayo Clinic. Sars-cov-2 (covid-19) vaccine, mrna (moderna) (intramuscular route).
Mayo Clinic. Sars-cov-2 (covid-19) vaccine, mrna (pfizer) (intramuscular route).
MedlinePlus. What are mRNA vaccines and how do they work?
Yuan Huang, Chan Yang, et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacologica Sinica, 2020. Vol. 41.
National Human Genome Research Institute. Understanding COVID-19 mRNA Vaccines.
Bojana Zizic. The COVID-19 vaccine does not change human DNA. Unicef. April 14, 2021.
Centers for Disease Control and Prevention. Adjuvants and Vaccines.
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