Clinical & translational immunology · 2026
CD56brightNK cells are negatively associated with antibody response to vaccination in people with multiple sclerosis on B-cell-depleting therapy.
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Perkins Griffith B, Hope Christopher M, Chai Cheng Sheng, Tunbridge Matthew J, Sterling Sebastian, Webb Kevin, Yap Joey, Yeow Arthur Eng Lip, Masavuli Makutiro G, Scaffidi Jacqueline, Zuiani James D, Akerman Anouschka, Aggarwal Anupriya, Milogiannakis Vanessa, Roberts Matthew B, Hurtado Plinio R, Turville Stuart, Grubor-Bauk Branka, Barry Simon C, Ravindran Janakan, Coates Patrick Toby, Hissaria Pravin
Аннотация
OBJECTIVES: We sought to identify determinants of vaccine response in people with multiple sclerosis (pwMS) receiving B-cell-depleting therapies.
METHODS: This was a prospective single-centre cohort study (ACTRN12623001249640). Peripheral blood samples were collected from pwMS receiving ocrelizumab (n = 38) before and after a third dose of COVID-19 mRNA vaccine. Immunogenicity was measured by T-cell IFN-γ ELISpot, antibody titres and live virus neutralisation. Humoral immunity was benchmarked against pwMS receiving natalizumab (n = 15), and against a correlate of real-world protection (50% reduction in incidence of infection). The peripheral immune phenotype was assessed by high-parameter flow cytometry and tested for association with vaccine response.
RESULTS: CD20+ T cells, natural killer (NK) cells and B cells were lower in pwMS receiving ocrelizumab, while CD27+CD38+ T-cell and CD8+ NK cell frequencies were elevated relative to natalizumab. Following a third dose, 51% of pwMS on ocrelizumab were seropositive for SARS-CoV-2 receptor-binding domain Ig, and 25% and 14% met the threshold for effective neutralisation of live ancestral and omicron BA.5 virus, respectively. B-cell frequency at the time of vaccination, but not time since ocrelizumab infusion, positively correlated with antibody response. Immunomodulatory CD56bright NK cells were negatively associated with antibody response. CD3-CD20+ B cells (% of lymphocytes) and CD56bright NK cells (% of NK cells) were associated with effective virus neutralisation in prior non-responders.
CONCLUSION: Time since ocrelizumab infusion was not associated with protective vaccination. Evaluation of B-cell and CD56bright NK cell frequencies may provide a personalised strategy to stratify pwMS for vaccination and prophylaxis.
METHODS: This was a prospective single-centre cohort study (ACTRN12623001249640). Peripheral blood samples were collected from pwMS receiving ocrelizumab (n = 38) before and after a third dose of COVID-19 mRNA vaccine. Immunogenicity was measured by T-cell IFN-γ ELISpot, antibody titres and live virus neutralisation. Humoral immunity was benchmarked against pwMS receiving natalizumab (n = 15), and against a correlate of real-world protection (50% reduction in incidence of infection). The peripheral immune phenotype was assessed by high-parameter flow cytometry and tested for association with vaccine response.
RESULTS: CD20+ T cells, natural killer (NK) cells and B cells were lower in pwMS receiving ocrelizumab, while CD27+CD38+ T-cell and CD8+ NK cell frequencies were elevated relative to natalizumab. Following a third dose, 51% of pwMS on ocrelizumab were seropositive for SARS-CoV-2 receptor-binding domain Ig, and 25% and 14% met the threshold for effective neutralisation of live ancestral and omicron BA.5 virus, respectively. B-cell frequency at the time of vaccination, but not time since ocrelizumab infusion, positively correlated with antibody response. Immunomodulatory CD56bright NK cells were negatively associated with antibody response. CD3-CD20+ B cells (% of lymphocytes) and CD56bright NK cells (% of NK cells) were associated with effective virus neutralisation in prior non-responders.
CONCLUSION: Time since ocrelizumab infusion was not associated with protective vaccination. Evaluation of B-cell and CD56bright NK cell frequencies may provide a personalised strategy to stratify pwMS for vaccination and prophylaxis.