For transplant recipients, third time may be the charm for better COVID vaccine protection

"Our findings suggest clinical trials are warranted to determine if transplant recipients should receive COVID-19 vaccine booster doses as standard clinical practice, similar to what is currently done with hepatitis B and influenza vaccinations for this population," says study lead author William Werbel, M.D., an infectious diseases research fellow at the Johns Hopkins University School of Medicine.

People who receive solid organ transplants (such as hearts, lungs and kidneys) often must take drugs to suppress their immune systems and prevent rejection. Such regimens may interfere with a transplant recipient's ability to make antibodies to foreign substances, including the protective ones produced in response to vaccines.

In the first of two previous studies, the researchers showed that only 17% of the participating transplant recipients produced sufficient antibodies after one dose. Then, in the second study, they found the level improved to 54% after the second shot. In both cases, even those transplant recipients with antibodies had levels well below what has been typically seen in people with healthy immune systems.

In their latest study, the researchers evaluated 30 organ transplant recipients who received a third dose of one of three vaccines -- Johnson & Johnson/Jansen, Moderna or Pfizer/BioNTech -- between March 20 and May 10, 2021. They had previously received two doses of either the Moderna or Pfizer/BioNTech vaccine. The median age of the study participants was 57, 17 were women and one identified as non-white. No study participant reported an illness prior to vaccination or a positive test for SARS-CoV-2. All were taking multiple immunosuppressive medications to prevent rejection of their transplanted organs.

"Our findings revealed that a third of the participants who had negative antibody levels and all who had low positive levels before the booster increased their immune response after a third vaccine dose," says study senior author Dorry Segev, M.D., Ph.D., the Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology and director of the Epidemiology Research Group in Organ Transplantation at the Johns Hopkins University School of Medicine.

A week after receiving their third vaccine dose, 23 study participants completed a questionnaire about adverse effects. Reactions were generally mild or moderate, with one participant reporting severe arm pain and another a severe headache. No participant reported fever or an allergic reaction. There was one case of mild organ rejection during the study.

"These reactions seem acceptable, considering the benefits that vaccines can confer," says Segev.

Werbel and Segev note that this study only examined antibody levels, and that future research is needed to see if the increased immune response after a third vaccine dose is associated with lower SARS-CoV-2 infection rates.

"Although the third vaccine dose appears to raise the immune response of transplant recipients to higher levels than after one or two doses, these people may still be at greater risk for SARS-CoV-2 infection than the general population who have been vaccinated," says Werbel. "Therefore, we recommend that transplant recipients and other immunocompromised people continue to wear masks, maintain physical distancing and practice other COVID-19 safety measures."

In addition to Werbel and Segev, the Johns Hopkins Medicine research team includes Brian Boyarsky, Michael Ou, Allan Massie, Aaron Tobian and Jacqueline Garonzik-Wang.

The study was supported by a donation from the Ben-Dov family; grants F32DK124941 and K23DK115908 from the National Institute of Diabetes and Digestive and Kidney Diseases; grant K24AI144954 from the National Institute of Allergy and Infectious Diseases; and grant gSAN-201C0WW from the Transplantation and Immunology Research Network of the American Society of Transplantation.