Publication: Science Advances

Kimia Kamelian, Benjamin Sievers, Michael Chen-Xu, Sam Turner, Mark Tsz, Kin Cheng, Mazharul Altaf, Steven A. Kemp, Adam Abdullahi, Kata Csiba, Dami A. Collier, Petra Mlcochova, Bo Meng, Rachel B. Jones, The CITIID-NIHR BioResource COVID-19 Collaboration, Derek Smith, John Bradley, Kenneth G. C. Smith, Rainer Doffinger, Rona M. Smith and Ravindra K. Gupta.

12 February 2025


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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