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Sci Adv . Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression

tetano

Editor, Senior Moderator
Sci Adv


. 2025 Feb 14;11(7):eadq3342.
doi: 10.1126/sciadv.adq3342. Epub 2025 Feb 12. Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression

Kimia Kamelian[SUP] 1 2 [/SUP], Benjamin Sievers[SUP] 2 [/SUP], Michael Chen-Xu[SUP] 1 3 [/SUP], Sam Turner[SUP] 4 [/SUP], Mark Tsz Kin Cheng[SUP] 1 [/SUP], Mazharul Altaf[SUP] 1 [/SUP], Steven A Kemp[SUP] 2 [/SUP], Adam Abdullahi[SUP] 2 [/SUP], Kata Csiba[SUP] 1 [/SUP], Dami A Collier[SUP] 1 2 [/SUP], Petra Mlcochova[SUP] 2 [/SUP], Bo Meng[SUP] 2 [/SUP], Rachel B Jones[SUP] 3 [/SUP]; CITIID-NIHR BioResource COVID-19 Collaboration; Derek Smith[SUP] 4 [/SUP], John Bradley[SUP] 1 5 [/SUP], Kenneth G C Smith[SUP] 6 7 [/SUP], Rainer Doffinger[SUP] 8 [/SUP], Rona M Smith[SUP] 1 3 5 [/SUP], Ravindra K Gupta[SUP] 1 2 9 [/SUP]



Affiliations
Abstract

Immune suppression poses a challenge to vaccine immunogenicity. We show that serum antibody neutralization against SARS-CoV-2 Omicron descendants was largely absent post-doses 1 and 2 in individuals with vasculitis treated with rituximab. Detectable and increasing neutralizing titers were observed post-doses 3 and 4, except for XBB. Rituximab in vasculitis exacerbates neutralization deficits over standard immunosuppressive therapy, although impairment resolves over time since dosing. We observed discordance between detectable IgG binding and neutralizing activity specifically in the context of rituximab use, with high proportions of individuals showing reasonable IgG titer but no neutralization. ADCC response was more frequently detectable compared to neutralization in the context of rituximab, indicating that a notable proportion of binding antibodies are non-neutralizing. Therefore, use of rituximab is associated with severe impairment in neutralization against Omicron descendants despite repeated vaccinations, with better preservation of non-neutralizing antibody activity.


 
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