• The U.S. Centers for Disease Control and Prevention (CDC) approved a second COVID-19 booster shot of the messenger RNA (mRNA) vaccines for people over 50 years old and those who are immunocompromised.
• Recent studies found most people who were immunocompromised had a strong immune response to mRNA vaccines for COVID-19.
• With the omicron variant waning and COVID-19 control measures ending, now is an ideal time to get up to date on vaccinations before new variants arise.

The CDC is now recommending a second booster shot for older adults and people with immunocompromised conditions. Those who are immunocompromised, people over 65, and people over 50 with underlying medical conditions are at increased risk for severe disease and hospitalization with COVID-19. These new public health recommendations come after recent studies showed a strong immune response to the Moderna and Pfizer vaccines in many immunocompromised people.

The New Recommendations

Health officials at the U.S. Food and Drug Administration (FDA) and CDC have authorized a second booster shot of the COVID-19 vaccines for people 50 and over and those with immunocompromising conditions. Although this recommendation affects a similar age group as initial recommendations for the first booster dose, there are several details to know before you get this fourth dose:

• This additional booster is for people who received their first booster shot or last COVID-19 vaccine shot at least four months ago.
• This fourth shot will be of either the Moderna or Pfizer vaccines, not the Johnson & Johnson vaccine.
• Even if you were previously vaccinated with the Johnson & Johnson vaccine, it is now recommended that this next dose be a Moderna or Pfizer vaccine only.
• For those who are immunocompromised and received a three-dose primary vaccination followed by an initial booster, this additional vaccine booster would count as your fifth shot.

Response to the Moderna Vaccine

These recommendations follow promising new results about the effectiveness of the vaccines in immunocompromised people. A recent study from Moffitt Cancer Center included people diagnosed with blood cancers, like leukemia, and people with solid tumors in their organs. Researchers tested levels of antibodies, the proteins the immune system makes to help destroy a target. In this case, the antibodies were to the SARS-CoV-2 virus that causes COVID-19, made in response to the Moderna COVID-19 vaccine.

After the second vaccine dose, about 90 percent of the people in the study developed antibodies against the coronavirus. About 98 percent of people with solid tumors showed an antibody response, while nearly 85 percent of people with blood cancers responded.

The lowest response — around 30 percent — was seen among people with chronic lymphocytic leukemia or B-cell non-Hodgkin lymphoma who were also receiving immunosuppressive therapy. But their response was much higher — nearly 73 percent — when they were not receiving treatment at the time of vaccination.

People who had the following treatments generally had less response to the vaccine:

• Anti-CD20 monoclonal antibodies (including rituximab, sold as Rituxan) less than six months before vaccination
• Bruton tyrosine kinase inhibitors (such as ibrutinib, sold as Imbruvica) used to treat some types of lymphoma and leukemia
• P13K inhibitors (such as idelalisib, sold as Zydelig) used to treat a variety of cancers
• Venetoclax used to treat leukemia and lymphoma
• CD19 chimeric antigen receptor (CAR) T cell therapy used to treat leukemia, lymphoma, and multiple myeloma

People who had the following treatments had a stronger response to the vaccine:

• Autologous (self) stem cell transplants in the last year
• B-cell maturation antigen CAR T-cell therapies used to treat multiple myeloma
• Allogeneic (donor) stem cell transplants

Response to the Pfizer Vaccine

While this recent study only included people given the Moderna vaccine for COVID-19, other research has looked at the response of immunocompromised individuals to the Pfizer vaccine. These vaccines are based on the same technique. Both use a molecule called mRNA to teach cells how to make a protein that will trigger an immune system response and help prevent COVID-19.

In one study, antibody testing showed around 72 percent of people who were immunocompromised responded to the Pfizer vaccine. Another study showed immune system response in people with a wide variety of immunocompromising conditions was about 67 percent. However, people with some health conditions were much more responsive to the Pfizer vaccine than others. For instance:

• People with HIV made antibodies in response to the Pfizer vaccine 98.7 percent of the time (a similar rate as the general population).
• People with multiple myeloma responded nearly 80 percent of the time.
• About 45 percent of people with kidney transplants responded to the vaccine.

A study looking at both mRNA vaccines in immunocompromised people living with HIV or solid organ transplants found the Pfizer vaccine had a similar response rate (about 94 percent) to the Moderna vaccine (around 92 percent).

Why These Results Matter

Although these studies do not directly address third doses or booster shots, additional doses of mRNA vaccines may increase detectable antibodies in a similar way to the first and second doses. Other research tells us antibody levels are likely to decrease over time, so getting booster doses at recommended intervals is necessary — even for vaccinated people who made antibodies after their initial shots.

Simply making antibodies does not always translate to complete immunity from COVID-19 infection. The findings from these studies are a good sign that mRNA vaccines for COVID-19 can trigger strong responses, even from people with compromised immune systems. It’s evidence that vaccines can protect people at higher risk of severe infections.

According to the CDC, getting vaccinated is still the best way to protect yourself and slow the spread of the virus. If you are unvaccinated because you had an immunodeficiency or autoimmune disease, were being treated for cancer, or are an organ transplant recipient, this new research should give you confidence to speak with your health care provider about when a COVID-19 vaccine would be right for you.

With the CDC now recommending a second COVID-19 booster and the omicron variant declining, now is an excellent time to get vaccinated and give your body a chance to build up immunity before a possible next wave of the pandemic.

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