Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination

Background

Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short- and long-term vaccine responses after repeated vaccination under the influence of anti-TNF treatment.

Methods

We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs.

Results

Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially [...]

Conclusions

The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination.

Rights

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Cite

Citation style:
Buhre, J.S., Pongracz, T., Geisen, U.M., Schubert, M., Wang, W., Nouta, J., Obara, M., Lehrian, S., Rahmöller, J., Petry, J., Tran, F., Schreiber, S., Sümbül, M., Berner, D., Gerdes, S., Schirmer, J., Longardt, A.C., Hoff, P., Kalinke, U., Ludwig, R.J., Bartsch, Y.C., Hoyer, B.F., Wuhrer, M., Ehlers, M., 2025. Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination. Allergy 80, 423–439. https://doi.org/10.1111/all.16241
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