What Are the Differences Between the Pfizer and Moderna COVID-19 Vaccines?

As of April 2022, the US has two fully approved COVID-19 vaccines to help in the fight against the pandemic.

In the fight against the COVID-19 pandemic, pharmaceutical companies worked diligently to develop a vaccine. As of April 2022, the US Food and Drug Administration (FDA) generally advises Americans to get one of two preferred vaccines: from pharmaceutical company Pfizer or biotechnology company Moderna. (In some situations, people may also get the Johnson & Johnson vaccine, which is approved by the FDA under emergency use authorization, EUA.)

At the beginning of the US COVID-19 Vaccination Program in December 2020, the FDA authorized two vaccines for emergency use: the Pfizer vaccine and the Moderna vaccine. On August 23, 2021, the FDA granted full approval for the Pfizer-BioNTech vaccine. And the Moderna vaccine received full approval on January 31, 2022. Full approval means that these companies are allowed to market their vaccines under brand names. The Pfizer-BioNTech vaccine is marketed as Comirnaty, and the Moderna vaccine is called Spikevax.

It can be confusing to have different vaccines in use to protect against the same virus, so here's what you need to know about how the fully approved Pfizer and Moderna vaccines compare.

How Do the COVID-19 Vaccines Work?

Both vaccines are made using a technology called messenger RNA (mRNA).

An mRNA vaccine works by encoding a portion of the spike protein found on the surface of SARS-CoV-2, the virus that causes COVID-19, the Centers for Disease Control and Prevention (CDC) explains.

The vaccines actually use pieces of the encoded protein to spark an immune response in your body. As a result, your body produces antibodies to SARS-CoV-2—proteins made by your immune system to help fend off future illnesses by the virus. Once your body creates that immune response, both the protein and mRNA are eliminated, while the antibodies stick around to protect you in the future.

According to Pfizer, these mRNA vaccines are different from conventional vaccines (like the flu vaccine) in that most conventional vaccines against viral disease are made from viruses grown in chicken eggs or other mammalian cells. No virus is needed to make a batch of an mRNA vaccine (though a small amount of the virus is used for gene sequencing and vaccine testing).

The body also responds to conventional vaccines versus mRNA vaccines in a slightly different way. With conventional vaccines, the antigen, or a piece of the virus, is injected into the body to form specific antibodies for the next time the body encounters that specific virus. However, in mRNA vaccines, the RNA provides instructions to the body's cells to produce antigens. Those cells then present the antigens to the body's immune system, prompting T-cell and antibody responses to fight the disease, per Pfizer.

How Effective Is Each Vaccine?

Each mRNA vaccine is the most effective after two primary doses. An assessment published in JAMA Network Open in June 2021 found that the Pfizer vaccine is 54% effective against symptomatic COVID-19 after the first dose. After the second dose, the vaccine is 95% effective, per the World Health Organization (WHO). The vaccine also has a high efficacy rate in people regardless of sex, age, and race, according to WHO recommendations from June 2021.

According to a February 2021 study published in the New England Journal of Medicine, the Moderna vaccine is about 94.1% effective against COVID-19 in people ages 18 and older in a trial of 30,000 people. And while there is a small difference in efficacy, it's not by much. "They both work," Derek Sant'Angelo, PhD, professor and associate director of basic science at the Rutgers Robert Wood Johnson Medical School, told Health.

(Compared to these two mRNA vaccines with over 90% efficacy, the Johnson & Johnson viral vector vaccine is over 66% effective.)

What Are the Side Effects of Each Vaccine?

As with any vaccine, some minor side effects are to be expected. In a fact sheet provided by the FDA regarding the Pfizer vaccine, the following side effects are listed as a possibility:

  • Injection site pain, swelling, or redness
  • Tiredness
  • Headache
  • Muscle pain
  • Chills
  • Joint pain
  • Fever
  • Nausea
  • Swollen lymph nodes

Pfizer also warns that there is a "remote chance" the vaccine could cause a severe allergic reaction that usually shows up within a few minutes up to an hour of getting a dose. Those with a history of severe allergic reactions should have a risk assessment conducted for the vaccine, and it's recommended that vaccines are administered in a setting where medical treatment is available.

In an FDA briefing document regarding the Moderna vaccine, the following symptoms are listed as potential side effects:

  • Injection site pain, swelling, or redness
  • Tiredness
  • Headache
  • Muscle pain
  • Joint pain
  • Chills
  • Fever
  • Nausea/vomiting

What Are the Ingredients of Each Vaccine?

Technically, the companies behind each vaccine don't need to release specifics until the vaccine is authorized by the FDA. In the EUA phase, Pfizer and Moderna released their ingredients anyway. According to the CDC, when the vaccines were fully authorized, the name change did not come with any changes to either vaccine's formula. The Pfizer vaccine's ingredients include:

  • mRNA
  • Lipids
  • Potassium chloride
  • Monobasic potassium phosphate
  • Sodium chloride
  • Dibasic sodium phosphate dehydrate
  • Sucrose

Moderna vaccine's ingredients are:

  • mRNA
  • Lipids
  • Tromethamine
  • Tromethamine hydrochloride
  • Acetic acid
  • Sodium acetate
  • Sucrose

Generally speaking, the mRNA does the heavy lifting for the vaccine, while the lipids help deliver the mRNA to your body, and the other ingredients help with pH maintenance and stability of the vaccine. "At the end of the day, these two vaccines are pretty similar," Thomas Russo, MD, professor and chief of infectious disease at the University at Buffalo in New York, told Health. "There are proprietary tweaks between the two of them but, at the end of the day, they're very similar."

Rajeev Fernando, MD, an infectious disease specialist working in COVID-19 field hospitals across the country, agreed. "They're pretty much the same thing," Dr. Fernando told Health.

How Many Doses Does Each Vaccine Require, and When Is a Booster Necessary?

Each mRNA vaccine requires two doses, given a few weeks apart, said Dr. Fernando. These two doses are considered the primary vaccination series.

According to the CDC's Overview and Safety information, the Pfizer-BioNTech vaccine, Comirnaty, is administered intramuscularly (injected into the muscle—commonly the deltoid in the upper arm), in a series of two shots, spaced three to eight weeks apart. Similarly, the Moderna vaccine, Spikevax, is also administered intramuscularly as two doses spaced four to eight weeks apart.

While these vaccines remain to be effective after the primary two-dose series, they can lose some effectiveness over time. Booster shots can help improve the effectiveness of vaccines that have already been administered. As of April 2022, people who have been fully vaccinated are eligible for a booster shot at least five months after the primary COVID-19 vaccination series, so the CDC. Fully vaccinated means having received two doses of an mRNA vaccine or, in some cases, one dose of the viral vector vaccine. The Pfizer and Moderna mRNA vaccines are the vaccines of choice for booster shots, regardless of the vaccine administered during primary vaccination.

Overall, whether you get the Pfizer or Moderna vaccine—or another vaccine authorized by the FDA—experts recommend getting vaccinated, period. "Take what you can get," said Dr. Fernando. Dr. Russo agreed. "Grab it while you can," said Dr. Russo.

The information in this story is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. While Health is trying to keep our stories as up-to-date as possible, we also encourage readers to stay informed on news and recommendations for their own communities by using the CDC, WHO, and their local public health department as resources.

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