UToledo Study of Kidney Transplant Recipients May Improve Future Vaccines

UToledo Study of Kidney Transplant Recipients May Improve Future Vaccines

A study of transplant recipients undertaken in the early years of the COVID-19 pandemic may have implications for developing and improving future vaccines for immunocompromised individuals.

As COVID-19 vaccines from Moderna and Pfizer became widely available in 2021, researchers at The University of Toledo asked a fairly straightforward question: Which of the two vaccines would provide the best protection for individuals who had received a kidney transplant?

In general, their analysis found the Moderna vaccine elicited a slightly higher antibody response in those patients than did the Pfizer version.

The results, however, were intriguing not because they clearly showed one vaccine was better than the other, but rather because they presented hints about why.

"The differences we found between the two vaccines might have been super useful in 2020. At this point, it's more of a footnote," said Dr. Michael Rees, a transplant surgeon and professor of urology at UToledo. "What makes this research so interesting isn't comparing vaccine A against vaccine B. It's what we discovered about vaccines and the immune system's regulatory response."

You can think of the immune system as sort of like the pedals of a car, Rees said.

There's a gas pedal that activates the immune response to fight off pathogens and a brake pedal to regulate the immune system to make sure it doesn't spiral out of control and attack the body itself.

In the case of the initial round of COVID-19 vaccines, the version developed by Moderna was heavier on the gas. The Pfizer version was stronger on the brake.

"The way the Moderna vaccine works seems to rely on a different type of receptor than what the Pfizer vaccine does," Rees said. "Nobody has really identified this idea that the building block of the receptor might move the immune system toward activation or regulation, and our team's findings suggest that is a very important consideration."

In addition to the theory that the lower antibody response produced by the Pfizer vaccine was because of its bent toward regulation, the study also provided new clues about how the immune system regulates itself. The study suggests the immune systems of immunosuppressed patients have a stronger bias toward regulation than they do activation.

Results of the study, which was funded by a grateful transplant recipient at The University of Toledo Medical Center, were published earlier this year in the peer-reviewed journal Vaccines.

UToledo researchers focused specifically on kidney transplants because of the large number of transplant patients receiving care at UTMC.

Following a kidney transplant - or any other kind of organ transplant - patients require a lifetime of powerful immunosuppressant drugs to prevent their body from attacking the new organ.

Not only does that make them more vulnerable to infection, it also means transplant recipients often do not receive the same level of protection from vaccines compared to the general population, said Dr. Stanislaw Stepkowski, a professor of medical microbiology and immunology, and the study's senior author.

"There are about 400,000 people in the United States who are living with a transplanted organ. They need to be protected," he said. "Understanding why and how certain vaccines may have more potent regulatory effects would clearly help to design much better protocols for vaccination overall."

The research team is working toward a follow-up study in mice to more deeply evaluate how vaccines impact the immune system's regulatory response in immunocompromised individuals and how different dosing amounts and schedules might be able to provide stronger protection against COVID-19 and a host of other illnesses.

"We started exploring this for COVID-19 and individuals who were immunosuppressed specifically because of kidney transplantation, but these findings are general and may be widely applied in the future," Stepkowski said.