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An illustration of two vaccine syringes. The syringe on the left has COVID-19 Vaccine Third Dose written on it. The syringe on the right has COVID-19 Vaccine Booster Dose written on it. the syringes are surrounded by little question marks and coronavirus germs.

As the science and guidance around COVID-19 continues to evolve, you may find certain recommendations vague or confusing if you’re immunocompromised. Many people have questions about recommendations for “additional doses” of the COVID-19 vaccine in immunocompromised individuals and the “booster shot” for the general population.

In August 2021, the U.S. Food and Drug Administration (FDA) adjusted the emergency use authorizations (EUAs) for the Pfizer and Moderna vaccines to allow for an additional dose to be given to certain immunocompromised individuals. The amendment applies to solid organ transplant recipients or those diagnosed with conditions considered to have an equivalent level of immunocompromise.

The U.S. Centers for Disease Control and Prevention (CDC) expanded on this, noting that moderately to severely immunocompromised people should receive an additional dose, including those who have:

  • Been receiving active cancer treatment for tumors or cancers of the blood
  • Received and organ transplant and are taking medication to suppress the immune system
  • Received a stem cell transplant within the last two years or are taking medicine to suppress the immune system
  • Moderate or severe primary immunodeficiency (like DiGeorge syndrome, Wiskott-Aldrich syndrome)
  • Advanced or untreated HIV infection
  • Active treatment with high-dose corticosteroids or other drugs that may suppress your immune response

The recommendation does not apply to the one-dose Johnson & Johnson vaccine, which has been used in far smaller numbers in the United States than the mRNA vaccines. This may change, however, as more research becomes available.

The American College of Rheumatology (ACR) recommends that people with inflammatory or autoimmune rheumatic conditions who are on immunosuppressive or immunomodulating medication should get a third dose of the Pfizer or Moderna vaccine.

Read more about the ACR’s latest COVID-19 vaccine guidance.

Meanwhile, an August statement from the U.S. Department of Health and Human Services (HHS) outlined a plan for COVID-19 booster shots — for the general public, not just those who are immunocompromised — in the United States. Recognizing that many vaccines tend to wane in their protection over time, and that additional vaccine doses could be needed to provide long-term protection, experts concluded that a COVID-19 booster shot will be needed to maximize the vaccine’s protection and prolong its durability.

“We have developed a plan to begin offering these booster shots this fall subject to FDA conducting an independent evaluation and determination of the safety and effectiveness of a third dose of the Pfizer and Moderna mRNA vaccines and CDC’s Advisory Committee on Immunization Practices (ACIP) issuing booster dose recommendations based on a thorough review of the evidence,” per the statement.

HHS says it is prepared to offer booster shots for all Americans beginning the week of September 20 and starting eight months after an individual’s second dose. That means people who were fully vaccinated earliest in the vaccination rollout, such as health care providers and nursing home residents, will likely be eligible for a booster.

“We also anticipate booster shots will likely be needed for people who received the Johnson & Johnson (J&J) vaccine,” adds the statement. “Administration of the J&J vaccine did not begin in the U.S. until March 2021, and we expect more data on J&J in the next few weeks. With those data in hand, we will keep the public informed with a timely plan for J&J booster shots as well.”

What does all this mean for someone who’s already getting an additional COVID-19 vaccine dose because they’re immunocompromised? Is there any difference between that and the booster for the general population? And how often will you need additional shots?

Many questions remain, but here’s what we know about the guidance so far. Remember, it’s always best to speak to your doctor for recommendations tailored to your medical condition.

“Any person who has questions about the best vaccination strategy for themselves should engage a licensed health care professional who knows their medical history well and knows about the degree to which they are immunocompromised — and can help them navigate what might seem like confusing guidance around these additional doses,” David Aronoff, MD, Director of the Division of Infectious Diseases at Vanderbilt University School of Medicine in Nashville, Tennessee.

What’s the Difference Between the Third COVID-19 Vaccine Dose and a Booster Shot?

Technically there is no difference as of now. Both are simply an additional administration of the same dose of the currently available COVID-19 vaccine, similar to the second shot of the mRNA vaccines you receive. However, they are referred to differently because of their purpose.

“Booster vaccines are given when immunity lapses, to rebuild COVID-19 antibodies eight months after the last vaccine,” says Daniel Arkfeld, MD, a rheumatologist with Keck Medicine of USC. “In immunocompromised patients, we give an additional vaccine to help build more immunity [in the first place].”

In short, people who are immunocompromised — including those who are on treatment for cancer, have organ transplants, and have immunocompromising conditions or are on immunosuppressive medications — may not receive an adequate immune response to the initial COVID-19 vaccine and, therefore, need an additional dose to build more of the response.

Research has shown that vaccine effectiveness may be 59 to 72 percent among immunocompromised people versus 90 to 94 percent in non-immunocompromised people after two doses, per the CDC.

“The purpose of a third dose is to try to accomplish in these individuals what two doses accomplished in everybody else,” says Dr. Aronoff. “It’s essentially saying, ‘Because your immune system is suppressed, you may not respond normally to this vaccine. So for you, the normal regiment is a three-dose regimen, not a two-dose regimen.’”

That’s why many experts consider this additional dose a “third dose” in immunocompromised patients, and not necessarily a “booster shot.” In a fraction of immunocompromised patients, even three doses may not bolster a full immune response — but more data is needed to determine this.

On the other hand, it’s assumed that people who are not immunocompromised have an age-appropriate immune response, but that the immune response can wane over time. Consequently, this means that susceptibility to the SARS-CoV-2 virus can increase, too.

“The purpose of an additional [booster] dose of the vaccine in those individuals is to induce a reminder to the immune system that stimulates or boosts the original immune response to get an incredibly vigorous recall of immune memory and extraordinarily high antibody levels very quickly,” says Dr. Aronoff. “That’s what we mean by a booster shot. That boost is much more predictable in people who are not immunocompromised.”

When it comes to the mRNA vaccines, it is likely that the additional dose that anybody receives will be the same dose (and the same vaccine) that they got the previous two times, since the mRNA vaccines are two-dose vaccines.

The mixing and matching of vaccines (say, getting Pfizer as a first dose and Moderna as a second dose) has been used in Europe and other places, especially when there have been issues in supply, according Yale Medicine. In the United States, current public health recommendations suggest sticking with one type of mRNA vaccine for both doses. (Switching is permitted for the third those for immunocompromised people if necessary.)

Keep in mind that guidance does not currently include recommendations around the Johnson & Johnson vaccine. “The data may be coming, but for now they don’t recommend boosting the one-shot J&J vaccine,” says Dr. Arkfeld.

Will Immunocompromised Patients Need to Get a Third COVID-19 Vaccine Dose AND a Booster Shot?

Experts aren’t sure, but as of now, the answer is no.

At this time, if you get a third dose of the vaccine because you’re immunocompromised, you do not need to get a fourth dose after eight months. That said, the guidance around the COVID-19 vaccine is constantly changing as more data emerges about its efficacy in various scenarios.

“Most likely, a fourth vaccine dose will be needed in immunocompromised patients, but we’re waiting on data from studies,” says Dr. Arkfeld. “I expect that will probably happen.”

In terms of receiving your third dose, you should wait at least 28 days between your second and third doses, but your doctor will be able to best determine the right timing of vaccination, per the CDC. There is no maximum interval between when you get your second and third doses — meaning you can and should still get your third dose even if it’s been several months since your last shot.

“One thing that will be helpful in the future is reliable, commercially available blood tests that can tell us if someone has had a proper immune response to their vaccine,” says Dr. Aronoff. “That is a need moving forward.”

However, currently available antibody tests cannot guarantee this.

“It’s possible that for immunocompromised people, we will be able to tell them whether they’ve had a measurable response to the three doses of vaccine,” says Dr. Aronoff. “And if they did, it’s possible they won’t require an additional dose to boost that response — or it’s possible that they may need an additional dose just to mount any response to the vaccine.”

More research is needed to determine how often additional doses will be needed for the general population or for immunocompromised patients.

Will the Booster Shot Be Reformulated for New Variants?

It’s possible — and, in fact, it’s being explored. Pfizer has said that it is studying a new formulation of its vaccine that would target the Delta variant.

“While Pfizer and BioNTech believe a third dose of BNT162b2 has the potential to preserve the highest levels of protective efficacy against all currently tested variants including Delta, the companies are remaining vigilant and are developing an updated version of the Pfizer-BioNTech COVID-19 vaccine that targets the full spike protein of the Delta variant,” per a statement from BioNTech.

The data on vaccine efficacy against the Delta variant has varied. For instance, one August 2021 study in The New England Journal of Medicine found that the Pfizer vaccine was 88 percent effective against the Delta variant after two doses — but another August 2021 study (which has not been peer-reviewed yet) posted on MedRxiv found that the Pfizer vaccine offered 42 percent protection against symptomatic COVID-19 infection in July when the Delta variant surged in the United States. Researchers, however, found that the vaccine still remained 85 percent effective in preventing hospitalization from COVID-19 and 100 percent effective in preventing death among participants.

The vaccine continues to provide protection against the Delta variant, but it’s possible new formulations could make it even more effective.

“Vaccine manufacturers are developing vaccines against SARS-CoV-2 that better target the newer variants that seem to be more contagious and are infecting people who are previously vaccinated,” says Dr. Aronoff. “But right now, it seems clear that even the existing vaccines are protecting people against getting really sick or dying from even the Delta variant, assuming that the vaccinated people have normal immune responses.”

It’s possible that in the future, especially as new COVID-19 variants emerge, vaccines will be developed to target more transmissible or more dangerous variants. In a way, this is already done with the flu vaccine: The quadrivalent flu vaccine targets four currently circulating strains of the influenza virus, while the trivalent flu vaccines target three currently circulating strains. This is why you need a new flu shot each flu season.

Should You Get Antibody Testing to Determine the Need for a Booster Shot?

In short, no. At this time, antibody tests cannot provide enough information to tell you if you’re adequately protected against COVID-19 or not.

“There are many different antibody tests on the market,” says Dr. Aronoff. “Some are more reliable than others. But not all antibody tests on the market are testing for what we call neutralizing antibodies, which are really the most important antibodies in our blood.”

When neutralizing antibodies bind to the SARS-CoV-2 virus, they neutralize it and prevent the virus from binding to your body’s cells and causing an infection.

“Not every antibody that our body raises in response to either natural infection or vaccine is a strong neutralizing antibody, and not every commercial test for antibodies against the spike protein are measuring neutralizing antibodies,” says Dr. Aronoff. “There’s a lot of variability between different companies’ tests, their accuracy, what exactly they’re measuring, and what the units of measurement mean relative to each other as tests.”

In other words, it’s difficult to look at a numerical result from an antibody test and know whether you’re protected or in need of another vaccine dose. Plus, many of the different commercial tests use slightly different units of measurement and they have not been standardized, so the result of a test from one company may be hard to compare to the result of a test from another company.

“We need standardized, validated antibody tests so that experts know if a numerical result from a test is right, too high, too low, or is reflecting neutralizing antibody-based immunity,” says Dr. Aronoff. “That is critical and such tests exist, but mostly in research settings. What is needed is for this type of validated testing to move into the clinical arena.”

For now, your best bet is to follow the CDC’s guidance and your doctor’s recommendations for third vaccine doses and booster shots, rather than relying on an antibody test to guide you.

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