What Are the Differences Between the COVID-19 Vaccines?

Emily Boynton Fact Checked
COVID-19 vaccine vials and a needle

With news updates coming in a mile a minute, it’s understandable if you’re confused by or worried about the COVID-19 vaccines.

You want to make sure you and your family are protected, but you don’t know what that means when it comes to the different vaccine types.  

Dr. Shireesha Dhanireddy, director of the Infectious Disease Clinic at Harborview Medical Center, wants to clear up the confusion and set the record straight on effectiveness. 

Spoiler alert: All of the COVID-19 vaccines are highly effective at preventing hospitalizations and death.

What are the types of COVID-19 vaccines?

Currently, there are three types of vaccines that protect against SARS-CoV-2, the virus that causes COVID-19.

While each vaccine type uses a different method, they all train your immune system to recognize and attack the spike protein, a viral protein from the SARS-CoV-2 gene that studs the outside of the virus and helps it invade your cells. 

By introducing harmless copies of the spike protein to your cells, the vaccines teach your immune system to make antibodies that will protect you if you are exposed to the actual coronavirus. 

RNA vaccines

The RNA vaccines use genetic instructions for making the SARS-CoV-2 spike protein to train your body to protect you from disease. The Pfizer and Moderna vaccines fall into this category, and both require two shots to be effective.

How does it work?

RNA is genetic material that teaches your body how to make proteins. In SARS-CoV-2, the RNA contains instructions for making the spike protein. When you are given an RNA COVID-19 vaccine, your cells read these instructions and start to make the spike protein, Dhanireddy explains.

The newly created spike proteins trigger your immune response, and your body is able to create specific antibodies that identify and destroy SARS-CoV-2. This way, even if you’re exposed to the coronavirus, your body will be able to eliminate it, preventing severe illness.
After your body learns how to protect you, it discards the mRNA.

Protein vaccines

These vaccines use harmless SARS-CoV-2 spike proteins to activate your body’s immune response. This type of vaccine is used for whooping cough (pertussis) and hepatitis B, and Novavax is currently creating a protein vaccine to protect against COVID-19. This vaccine is still in clinical trials. 

If the process of how protein vaccines work sounds similar to RNA vaccines, it’s because it is.

“The vaccines use a different mechanism but overall have the same effect: to make anti-spike protein antibodies,” Dhanireddy says.

The key difference is that RNA vaccines teach your body to make the spike protein, whereas protein vaccines inject the protein directly into your body. In either case, the vaccine exposes you to a harmless spike protein that trains your cells to fight off infection and keep you safe. 

Virus vector vaccines

In this type of vaccine, a DNA copy of the SARS-CoV-2 gene that creates the spike protein is transported into your cells via a harmless virus, called a vector, Dhanireddy says.

Adenoviruses, which cause the common cold, are the vector for the COVID-19 vaccines. (But don’t sweat, scientists have engineered the adenovirus so that it can’t cause sickness, but can enter your cells and deliver the spike protein gene DNA copy.)

Your cells use the instructions in the DNA to make the spike protein, which stimulates your immune response. In turn, your body builds up antibodies that protect you from getting sick with COVID-19.
The vaccines manufactured by AstraZeneca and Johnson & Johnson use the vector approach. 

Are all the vaccines effective at protecting you from COVID-19?

When it comes to the quality of the COVID-19 vaccines, Dhanireddy could not be clearer. 

“All of these vaccines are highly effective,” she says. “All of them are highly effective at keeping people out of the hospital, keeping people from getting severe infection from COVID-19 and preventing death.”

The reason there has been some confusion about the effectiveness of the vaccines has to do with terminology. 
Efficacy refers to how well the vaccines prevent disease during clinical trials. Effectiveness, on the other hand, refers to how well the vaccines protect against severe illness and death in the real world.

While there have been slight differences in the efficacy of the vaccines to prevent mild symptoms, all of the vaccines have been shown to be both highly efficacious and effective in preventing serious illness and death. 

Dhanireddy notes this is a common phenomenon that is similar to other vaccines, like those that protect against the flu or pneumonia. While you can still get the flu or pneumonia if you are vaccinated, you will only get a mild case — not a severe flu or invasive pneumonia.

The bottom line? No matter what COVID-19 vaccine you receive, you can rest assured that you are protected from severe illness, hospitalization and death due to COVID-19.

Do all the COVID-19 vaccines protect against the new variants?

While all of the COVID-19 vaccines are highly effective against severe illness and death caused by the early strain of SARS-CoV-2, less is known about how effective they are against emerging variants of the virus. This is due in part because the Pfizer and Moderna vaccines were studied before the variants existed.

The virus variants have mutations that make them better at connecting to our cells, which makes it easier to spread the virus. These mutations might enable the virus variants to get around the immunity generated by the first vaccines. 

More information is still needed on how the Pfizer and Moderna vaccines fair against virus variants, but Dhanireddy stresses that any vaccine will still make a difference in protecting you from severe illness and death.  

How do the side effects of the different COVID-19 vaccines compare?

“There are no significant differences in the common side effects that exist among the three vaccines currently available,” Dhanireddy says. 

Common side effects in clinical trials for the vaccines include pain at the injection site, fatigue and low-grade fevers. Other side effects have included muscle and joint pain as well as headaches.

While unpleasant, these reactions won’t prevent daily activity for most people, Dhanireddy says. 

If you have a history of severe allergic reactions, be sure to let your doctor know. If possible, you can also plan to take a day off of work in case you aren’t feeling well.

Which COVID-19 vaccine is the best?

The best COVID-19 vaccine is the one that’s offered to you. 

While there are slight differences in efficacy, side effects and dosage, the reality is that all approved COVID-19 vaccines will save your life, keep you out of the hospital and help keep your community safe. 

“Our goal is to keep people out of the hospitals and keep them healthy — and the COVID-19 vaccines do that,” Dhanireddy says. 

Editor’s Note: This article was updated to reflect the April 13, 2021 recommendation by the FDA and CDC that administration of the Johnson & Johnson vaccine be paused. This action was based on a small number of cases of a rare and severe type of blood clot reported in people who received the J&J vaccine. Although this adverse event is very rare, safety is the highest priority for all COVID-19 vaccines, especially given their Emergency Use Authorization status.

The info in this article is accurate as of the publishing date. While Right as Rain strives to keep our stories as current as possible, the COVID-19 pandemic continues to evolve. It’s possible some things have changed since publication. We encourage you to stay informed by checking out your local health department resources, like Public Health Seattle King County or Washington State Department of Health.