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

Author:

Buhre Jana Sophia1,Pongracz Tamas2,Geisen Ulf Martin3,Schubert Mareike4,Wang Wenjun2,Nouta Jan2,Obara Maureen5,Lehrian Selina1,Rahmöller Johann1ORCID,Petry Janina1,Tran Florian67,Schreiber Stefan67,Sümbül Melike8,Berner Dennis3,Gerdes Sascha8,Schirmer Jan3,Longardt Ann Carolin9,Hoff Paula10,Kalinke Ulrich5ORCID,Ludwig Ralf J.1112,Bartsch Yannic C.4ORCID,Hoyer Bimba F.3,Wuhrer Manfred2,Ehlers Marc113ORCID

Affiliation:

1. Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine University of Lübeck and University Medical Center Schleswig‐Holstein Lübeck Germany

2. Center for Proteomics and Metabolomics Leiden University Medical Center Leiden The Netherlands

3. Medical Department 1, Rheumatology and Clinical Immunology University Medical Center Schleswig‐Holstein Kiel Germany

4. Laboratory of Anti‐viral antibody‐omics TWINCORE—Institute for Experimental Infection Research, Helmholtz Center for Infection Research (HZI) and Medical School Hannover (MHH) Hannover Germany

5. Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany

6. Institute of Clinical Molecular Biology, Christian‐Albrecht University of Kiel Kiel Germany

7. Department for Internal Medicine I University Medical Center Schleswig‐Holstein Kiel Germany

8. Department for Dermatology University Medical Center Schleswig‐Holstein Kiel Germany

9. Department of Pediatrics University Medical Center Schleswig‐Holstein Kiel Germany

10. Department of Rheumatology Endokrinologikum‐Gruppe Berlin Germany

11. Lübeck Institute of Experimental Dermatology University of Lübeck Lübeck Germany

12. Department of Dermatology University Medical Center Schleswig‐Holstein Lübeck Germany

13. Airway Research Center North (ARCN) University of Lübeck, German Center for Lung Research (DZL) Lübeck Germany

Abstract

AbstractBackgroundRecently, 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.MethodsWe 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.ResultsAnti‐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 generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti‐TNF‐treated patients, especially in the elderly. The reduced short‐ and long‐term IgG (1) levels in anti‐TNF‐treated patients correlated with diminished functional activity and an increased risk for the development of COVID‐19.ConclusionsThe 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.

Publisher

Wiley

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