When healthy people get vaccinated against COVID-19, they can feel confident that they are well-armored against the virus.
For individuals with compromised immune systems, however, it’s not nearly as straightforward.
Studies have shown that some immunosuppressed patients develop a robust antibody response. Others develop no response at all.
“That variation in immune response is one of the biggest questions we are facing,” said Dr. Stanislaw Stepkowski, a transplant immunologist and professor in The University of Toledo College of Medicine and Life Sciences. “It’s the same vaccine, the same dose, but it’s not protecting everyone at the same level.”
Stepkowski suspects the answer lies with the specific types of antibodies being produced after vaccination — and how the body’s immune cells are responding and working together to produce them.
“When we hear stories on the news about vaccine effectiveness, we often hear references to antibody production, but that’s a very general statement,” he said. “In reality, you can divide this into different quality of antibodies. We have IgM, IgG and IgA. The working hypothesis is that patients who produce all of those antibodies have the best protection.”
With $700,000 in support from an anonymous donor, Stepkowski is leading a UToledo research team that will monitor the level of those three key antibodies in hundreds of patients who received a kidney transplant at The University of Toledo Medical Center.
Through that, the team hopes to learn more about how the COVID-19 vaccine confers protection in specific individuals and provides valuable insights about how clinicians might tweak the dosage or delivery method of the vaccine to better protect those with suppressed or compromised immune systems.
Individuals who have weakened immune systems are more likely to get severely sick if they contract COVID-19, regardless of why they are immunocompromised.
Those who have received an organ transplant — including a kidney — require a lifelong cocktail of immunosuppressive drugs to prevent their bodies from rejecting the new organ.
“While these medications are wonderful at stopping rejection, they impede the immune system’s ability to fight off diseases like COVID. They also impair the body’s ability to respond to a COVID vaccination,” said Dr. Michael Rees, a transplant surgeon at UTMC and professor of urology in the UToledo College of Medicine and Life Sciences.
Rees, who is collaborating with Stepkowski on the project, said only half of immunosuppressed patients have an immune response of any kind following full vaccination. While booster doses can improve their immune response, only about a third of those who had no response to the initial vaccine course generated antibodies after getting a booster dose.
IgM is the first antibody the body produces to fight against viral and bacterial infections. IgM is produced exclusively by a type of white blood cell called B-cells.
Production of IgG and IgA antibodies require a more specialized immune response, with B-cells and T-cells working together.
Part of the study will investigate how individuals’ T-cells are responding to the COVID-19 vaccine. It’s possible, Stepkowski said, that the reason some immunosuppressed individuals don’t develop a robust response to vaccination is rooted in how their T-cells are functioning.
Each transplant recipient will have their blood tested for these antibodies four times over the course of the study. Researchers will be comparing those levels to samples drawn from healthy volunteers.
Rees said researchers also will assess if additional booster shots help those immunosuppressed transplant patients who did not respond after the first booster.
“This study will help us better understand the full spectrum of responses of immunosuppressed transplant patients to the COVID vaccine,” Rees said. “I am very happy that The University of Toledo has been chosen to do these important studies to try to help us better understand how to protect transplanted patients.”
Beyond evaluating the specific antigen makeup, faculty scientists in the Department of Medical Microbiology and Immunology will run tests on each collection of antibodies to see how well they neutralize the SARS-CoV-2 virus, including the more transmissible delta variant.
“This is work that matters and is important,” Stepkowski said. “It’s not just science that goes on the shelf, but science that is immediately applicable.”