A recent study investigated the evolution of the SARS-CoV-2 antibody repertoire following successive mRNA vaccinations in immunosuppressed patients.
In the study, published in eBioMedicine, investigators analyzed 878 participants, including healthy controls and patients with immune-mediated inflammatory diseases (IMID) receiving different immunosuppressive treatments,
They tracked serum antibody titers against the receptor-binding domain (RBD) of the Wuhan-Hu-1 (WH1) strain and the Omicron BA.1 variant across three mRNA vaccine doses. The study observed increasing anti-BA.1 RBD reactivity over time, particularly following the third vaccination, which was attributed to affinity maturation as measured by inhibition of angiotensin-converting enzyme 2 (ACE2)-RBD interactions.
The investigators found that methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors did not significantly alter cross-variant antibody evolution, whereas anti-CD20 therapy did.
Patients treated with MTX or TNF inhibitors exhibited trends in antibody evolution similar to those of healthy individuals, showing increased BA.1 RBD cross-reactivity following three vaccine doses. However, patients receiving anti-CD20 therapy showed minimal to no antibody evolution, suggesting that repeated mRNA vaccination may not elicit broad cross-variant protection in this patient population.
Prior SARS-CoV-2 infections accelerated the emergence of BA.1 RBD reactivity following the first two vaccinations but did not lead to a significantly different response compared with vaccination alone following three doses.
"Similar trends were seen in patients treated with MTX and/or TNF [inhibitors], but not in patients on anti-CD20 therapy. SARS-CoV-2 infections prior to vaccination accelerated these effects initially while leading to comparable results after three vaccinations," said lead study author Jim B.D. Keijser, of the Department of Immunopathology at the Sanquin Research and Landsteiner Laboratory in Amsterdam, and his colleagues.
These findings may contribute to refining vaccination strategies among patients with IMIDs.
Full disclosures are detailed in the study.
