期刊
NATURE MEDICINE
卷 27, 期 11, 页码 1990-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01507-2
关键词
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资金
- National Institutes of Health (NIH) [AI105343, AI082630, AI108545, AI155577, AI149680, AI152236, P30-AI0450080, R01 AI118694, UC4 DK112217, T32 AR076951-01, T32 CA009140, U19AI082630, UM1 AI144288, NMSS SI-2011-37160]
- Allen Institute for Immunology
- Chen Family Research Fund
- National Multiple Sclerosis Society-American Brain Foundation Clinician Scientist Award
- Parker Institute for Cancer Immunotherapy
- Penn Center for Research on Coronavirus and Other Emerging Pathogens
- University of Pennsylvania Perelman School of Medicine COVID Fund
- University of Pennsylvania Institute for Immunology Glick COVID-19 research award
- University of Pennsylvania Perelman School of Medicine 21st Century Scholar Fund
- NIH [75N9301900065]
Patients with multiple sclerosis on anti-CD20 monotherapy exhibit significantly reduced SARS-CoV-2-specific antibodies and memory B cells, while CD4(+) and CD8(+) T cells are robustly activated compared to healthy controls after receiving BNT162b2 or mRNA-1273 mRNA vaccination.
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T-FH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T(H)1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T-FH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20. SARS-CoV-2-specific antibodies and memory B cells are significantly reduced, but CD4(+) and CD8(+) T cells are robustly activated, in patients with multiple sclerosis on anti-CD20 monotherapy versus healthy controls after BNT162b2 or mRNA-1273 mRNA vaccination.
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