Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression
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.
Authors
- Kenneth G. C. Smith (ORCID: https://orcid.org/0000-0003-3829-4326)
- Kimia Kamelian (ORCID: https://orcid.org/0000-0003-3465-1285)
- Rainer Döffinger
- Derek J. Smith (ORCID: https://orcid.org/0000-0002-2393-1890)
- Adam Abdullahi (ORCID: https://orcid.org/0000-0001-9703-8264)
- Ravindra K. Gupta (ORCID: https://orcid.org/0000-0001-9751-1808)
- Mark T. K. Cheng (ORCID: https://orcid.org/0000-0003-4323-5574)
- S. Richard Turner (ORCID: https://orcid.org/0000-0003-0168-5497)
- Dami A. Collier (ORCID: https://orcid.org/0000-0001-5446-4423)
- Rachel Bronwen Jones (ORCID: https://orcid.org/0000-0003-4790-283X)
- Petra Mlčochová (ORCID: https://orcid.org/0000-0001-6908-9363)
- Steven A. Kemp (ORCID: https://orcid.org/0000-0001-7077-6793)
- John R. Bradley (ORCID: https://orcid.org/0000-0002-7774-8805)
- Rona Smith (ORCID: https://orcid.org/0000-0002-7438-5156)
- Benjamín L. Sievers (ORCID: https://orcid.org/0000-0002-9681-9082)
- M. Chen-Xu
- Kata Csiba
- Bo Meng (ORCID: https://orcid.org/0000-0001-5668-2221)
- Mazharul Altaf
Institutions
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- University of Cambridge (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Cambridge School (PT)
- Plastic Logic (United Kingdom) (GB)
- Africa Health Research Institute (ZA)
- Addenbrooke's Hospital (GB)
Publication Details
- Journal
- Science Advances
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1126/sciadv.adq3342
- Citations
- 3
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 4.19
Funders
- GlaxoSmithKline
- Vasculitis UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- NIHR Cambridge Biomedical Research Centre