COVID-19 Boosters: The Latest Advice

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As the COVID-19 pandemic continues, additional—or booster—doses of the vaccine are now being recommended. Photo by Getty Images.

[Originally published: July 27, 2021. Updated: Feb. 14, 2022.]

Yale Medicine

Carrie MacMillan

Note: Information in this article was accurate at the time of original publication. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.

Even though it seems like only yesterday people were calculating the date they could feel fully protected by their vaccination, boosters are increasingly being recommended for wider swaths of the population.

In mid-November, the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) said all adults 18 or older are eligible for a booster shot six months after completing their primary vaccination series if they started with Pfizer-BioNTech or Moderna—or two months after getting the Johnson & Johnson single-shot vaccine.

In early December, the FDA authorized (and CDC approved) the Pfizer booster for 16- and 17-year-olds. But for J&J recipients, the advice changed in mid-December when the CDC recommended that vaccines other than J&J’s should be preferred, citing links between the vaccine and a rare blood clotting disorder.

The booster momentum continued when the FDA and CDC, in early January, recommended a booster dose of the Pfizer vaccines for adolescents ages 12 to 15 at least five months after the second dose. Previously, the interval had been at least six months between second dose and booster. Now, the CDC recommends a five-month interval for both Pfizer and Moderna. (Moderna is only authorized for ages 18 and up.)

Meanwhile, boosters have remained increasingly important as the highly contagious Omicron variant continues to spread quickly.

“People get confused—or they think something is wrong—when guidance changes with COVID-19, but we have to remember that we are learning about this as we go.”

— Albert Shaw, MD, PhD, Yale Medicine infectious diseases expert

COVID-19 booster shots are not a new idea. Since the vaccines were first introduced last December, scientists have acknowledged that boosters may someday be needed.

“The main question is how long the immunologic protection against SARS-CoV-2, which causes COVID-19, lasts,” says Albert Shaw, MD, PhD, a Yale Medicine infectious disease specialist. “And since we are learning about COVID-19 in real time, this is hard to know definitively.”

The recommendation of boosters doesn’t represent a failure of the existing vaccines, Dr. Shaw notes. “People get confused—or they think something is wrong—when guidance changes with COVID-19, but we have to remember that we are learning about this as we go,” he says.

We compiled a list of booster-related questions to ask Dr. Shaw. His answers are below.

What is a booster?

“The simplest answer is that it’s just another dose of a vaccine you received,” Dr. Shaw explains. “The concept is to prolong protective immunity, particularly if there is evidence that protection is waning after a period of time.”

Most children receive routine vaccinations, including boosters, for illnesses such as chickenpox, tetanus, diphtheria, mumps, measles, and rubella—to name a few. “These vaccine series, as we call them, are recommended because you need the extra doses to get longer lasting protective immunity,” Dr. Shaw says.

There is also a technical distinction between the terms “third dose” and “booster.”

Doctors use the term third dose when referring to people with compromised immune systems who may not have gotten the level of protection they need from the first two doses. The third dose provides that level of immunity.

A booster shot is recommended due to concern that the effectiveness of the vaccine decreases over time and may not protect against a new strain. A booster may be given to older people or those with chronic medical conditions or other risk factors.

Why do we need a booster for COVID-19?

While a booster sometimes is an exact replica of the initial vaccine, it can also be tweaked. With COVID-19, this is key because the vaccine could then be tailored to target particular variants of the virus.

“The current vaccines are still effective against the variants we are now seeing, particularly for protecting against serious illness that would require hospitalization or cause death. But if the virus evolves further and there is a worse variant, the vaccine could be modified,” Dr. Shaw says.

One of the great things about the mRNA technology, which the Pfizer and Moderna vaccines use, Dr. Shaw notes, is that it’s easy to change them up to match variants, and they can be quickly produced at scale. “This is different from the manufacturing process for the most commonly used flu vaccines, which is a much slower process because influenza virus strains need to be grown in chicken eggs, from which a particular viral protein is purified and formulated into a vaccine,” he says.

How do we know if we need a booster?

It is normal for virus-fighting antibodies—such as those that are stimulated by a COVID-19 vaccine—to wane over time. Monitoring antibody levels in the blood is one way to measure vaccine efficacy and research has found that protection remains high for six months after the second shot of a Pfizer or Moderna vaccine. However, some studies have shown a decline in antibody levels among vaccinated individuals beyond that point.

“You can certainly look at antibody levels, and that does offer some indication of how much protection lasts. But even if they have waned, that doesn’t necessarily mean the body’s capacity to respond to exposure is gone,” Dr. Shaw says. “One of the most amazing parts of the immune system is immunologic memory of past infections or vaccines. If you are re-exposed to something [via a booster shot, that follows the original exposure by vaccination], the memory response is even more vigorous than the original. This memory response includes antibody responses, but also includes an additional arm of the immune system controlled by a different group of white blood cells called T cells or T lymphocytes.”

T cell immune responses are especially important for viral infections like those with SARS-CoV-2, but are more difficult to study than antibody responses outside of a research laboratory setting, adds Dr. Shaw. “However, T cell responses may prove to be just as important as antibody responses in protecting against infection or against serious disease requiring hospitalization,” he says.

Can you ‘mix and match’ vaccines in a booster?

So-called “mixing and matching” of vaccines (a first dose of Pfizer, followed by a second dose of Moderna, for example, to complete the mRNA two-dose series) has been used in Europe and other places, particularly when there were supply issues.

And there have been studies suggesting this approach—with one dose of AstraZeneca’s vaccine (which is not available in the U.S.) and one dose of Pfizer’s vaccine—may even offer more vigorous protection. But here in the U.S., the current public health recommendations are that people should stick with one type of mRNA vaccine for both doses.

But what about for boosters—if they are recommended, should you stick with your original kind?

The FDA and CDC now support a “mix-and-match” approach that allows people to choose a different vaccine for their booster than the one they started with. However, the CDC now says mRNA vaccines are preferred over J&J as a booster in most situations, though J&J can still be considered in some situations.

Can a booster cause more—or worse—side effects?

If you were among the unlucky recipients who felt really ill or had any of the rare but largely harmless reactions to your initial COVID-19 vaccination, you may be leery of the idea of a third dose, in case it causes a similar or worse reaction.

But according to the FDA, the most commonly reported side effects by individuals who received a booster dose included pain, redness, and swelling at the injection site; fatigue; headache; chills; and muscle or joint pain. Swollen lymph nodes in the underarm were observed more frequently following the booster dose than after the second dose.

The FDA has been examining information about the risk of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the outer lining of the heart) following vaccination with mRNA vaccines, and has determined the benefits of a booster outweigh the risk of either condition.

Are those who are immunocompromised eligible for a booster or a third dose?

Last summer, the FDA amended the emergency use authorizations (EUA) for Pfizer and Moderna to allow a third dose of their COVID-19 vaccines for certain immunocompromised people. (An EUA is given to products during public health emergencies, but is not a traditional approval. Although Pfizer and Moderna have been given full authorization for their vaccines for ages 16 and 18 and up, respectively, boosters from all three vaccine manufacturers are still under an EUA.)

The list for immunocompromised people who are eligible for additional doses include solid organ transplant recipients and those with conditions that give them an equally reduced ability to fight infections and other diseases. A third dose of the Pfizer or Moderna vaccines may increase protection in this vulnerable population, according to data the FDA evaluated.

Furthermore, the CDC now says that moderately and severely immunocompromised people who are 18 and older should receive a booster dose of a COVID-19 mRNA vaccine at least three months after their third dose.

In early January, the FDA and CDC recommended a third Pfizer dose for immunocompromised children ages 5 to 11 at least 28 days following their second dose.

Should we first be vaccinating the world?

There is also a moral element to the question of booster shots, with some public health officials saying the focus should be on vaccinating more of the world’s population first before giving supplementary doses to those who already have some protection.

Dr. Shaw says he understands this sentiment. “On this planet, we are all interdependent and we can see that many of these variants originated outside the U.S. That certainly speaks to the need to vaccinate the world, especially to drive down infection rates that support the emergence of new variants,” he says. “Ultimately, this is what needs to be done to end the pandemic.”

[Visit Yale Medicine’s Vaccine Content Center for more stories on COVID-19 vaccines.]

Note: Information provided in Yale Medicine articles is for general informational purposes only. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider with any questions you have regarding a medical condition.