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Additional COVID-19 vaccine doses may ‘bully’ response in immunosuppressed patients

Photo Illustration by Erin O'Flynn/The Daily Beast/Getty

Additional COVID-19 vaccine doses can occasionally “bully” a humoral response in patients who are immunocompromised, according to a presenter at the 2023 Biologic Therapies Summit.

“Most immunosuppressed people can mount a decent humoral antibody response within 2 weeks of the second dose of a SARS-CoV-2 vaccine,” Alfred Kim, MD, Ph.D., assistant professor of medicine in the division of rheumatology at Washington University in St. Louis, told attendees at the hybrid meeting.

That said, Kim raised several relevant questions that still require more detailed analysis and assessment. “When is the best time to administer COVID-19 vaccines relative to the last dose of B-cell-depleting medications?” he asked. “What about T cells? Are they functional? Do they protect against COVID-19 by themselves?”

Patients receiving B-cell-depleting therapies will demonstrate the weakest antibody response, followed by those on mycophenolate mofetil (MMF), glucocorticoids, Janus kinase inhibitors, then TNF inhibitors. Kim focused on B-cell depleting therapies, MMF, and TNF inhibitors as particularly challenging areas.

The key to B-cell-depleting therapies is the timing of the dose, according to Kim. “Those vaccinated within 6 months of the last dose of B-cell depleting therapy mount a poor response,” he said. “Those vaccinated more than 6 months out did much better.”

This raises the question of whether T cells can serve in a “rescue” role if B cells are not present. “Data suggested that T cells are generated and function against the spiked antigen,” Kim said.

However, whether this could be functional in breakthrough infections remains to be seen. “The data suggest it would not be sufficient,” Kim said. “The totality of data does not suggest breakthrough infection protection, but the jury is out.”

Although some experts have suggested that more vaccine doses may solve this problem, the data has been inconclusive, he added. A study in Norway employed this strategy but the results showed “poor antibody titers after a third dose,” according to Kim.

Further studies of COVID-19 vaccination dose timing in the B-cell depletion setting are needed, he noted. Meanwhile, the story for MMF “appears to be a bit more optimistic,” Kim reported.

“Additional doses do seem to be beneficial,” he said. “It appears you can just bully the immune system aside with extra doses. We really need to keep pushing our patients to get that fourth dose.”

Regarding TNF inhibitors, Kim suggested that there are “admittedly unclear clinical consequences” associated with mounting a humoral response to COVID-19 vaccination.

Patients taking these medications may have an inability to “diversify antibody response” or “cross-variant neutralize,” according to some data sets, he said.

“Those on TNF inhibitors are in a uniquely disadvantageous position,” Kim added. That said, data from the pre-omicron era provide some reassurance that vaccine responses could improve again for patients using TNF inhibitors.

“If we gave TNF inhibitor users a third dose of vaccination, they were able to mount antibody titers to all the antibodies we assessed,” Kim said. “There is more to understanding immune response than just measuring titers.”

However, Kim described omicron as “evasive,” which presents challenges for patients on all of the aforementioned medications. “Clinically, we are not sure how to frame this yet,” he said. “The clinical implications are still a little unclear.”

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