Lower magnitude and faster waning of antibody responses to SARS-CoV-2 vaccination in anti-TNF-α-treated IBD patients are linked to lack of activation and expansion of cTfh1 cells and impaired B memory cell formation

作者：Erika Garner‐Spitzer, Angelika Wagner, Venugopal Gudipati, Anna-Margarita Schoetta, Maria Orola-Taus, Michael Kundi, Renate Kunert, P. M. Mayrhofer, Johannes B. Huppa, Hannes Stockinger, Rita Carsetti, Pia Gattinger, Rudolf Valenta, Bernhard Kratzer, Al Nasar Ahmed Sehgal, Winfried F. Pickl, Walter Reinisch, Gottfried Novacek, Ursula Wiedermann · 发表于：EBioMedicine · 年份：2023 · DOI：10.1016/j.ebiom.2023.104788 · 被引用次数：25 · 研究领域：SARS-CoV-2 and COVID-19 Research、T-cell and B-cell Immunology、Immune responses and vaccinations

BACKGROUND: Patients with inflammatory bowel disease (IBD) and healthy controls received primary SARS-CoV-2-mRNA vaccination and a booster after six months. Anti-TNF-α-treated patients showed significantly lower antibody (Ab) levels and faster waning than α4β7-integrin-antagonist recipients and controls. This prospective cohort study aimed to elucidate the underlying mechanisms on the basis of circulating T-follicular helper cells (cTfh) and B memory cells. METHODS: We measured SARS-CoV-2- Wuhan and Omicron specific Abs, B- and T-cell subsets at baseline and kinetics of Spike (S)-specific B memory cells along with distributions of activated cTfh subsets before and after primary and booster vaccination. FINDINGS: Lower and faster waning of Ab levels in anti-TNF-α treated IBD patients was associated with low numbers of total and naïve B cells vs. expanded plasmablasts prior to vaccination. Along with their low Ab levels against Wuhan and Omicron VOCs, reduced S-specific B memory cells were identified after the 2nd dose which declined to non-detectable after 6 months. In contrast, IBD patients with α4β7-integrin-antagonists and controls mounted and retained high Ab levels after the 2nd dose, which was associated with a pronounced increase in S-specific B memory cells that were maintained or expanded up to 6 months. Booster vaccination led to a strong increase of Abs with neutralizing capacity and S-specific B memory cells in these groups, which was not the case in anti-TNF-α tre...