tetano
Editor, Senior Moderator
Nat Med
. 2021 Sep 14.
doi: 10.1038/s41591-021-01507-2. Online ahead of print.
Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy
Sokratis A Apostolidis[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Mihir Kakara[SUP] #[/SUP][SUP] 4 5 [/SUP], Mark M Painter[SUP] #[/SUP][SUP] 1 3 6 [/SUP], Rishi R Goel[SUP] #[/SUP][SUP] 1 3 6 [/SUP], Divij Mathew[SUP] 1 3 6 [/SUP], Kerry Lenzi[SUP] 5 [/SUP], Ayman Rezk[SUP] 4 5 [/SUP], Kristina R Patterson[SUP] 4 5 [/SUP], Diego A Espinoza[SUP] 4 5 7 [/SUP], Jessy C Kadri[SUP] 4 5 [/SUP], Daniel M Markowitz[SUP] 4 5 [/SUP], Clyde E Markowitz[SUP] 4 5 [/SUP], Ina Mexhitaj[SUP] 4 5 [/SUP], Dina Jacobs[SUP] 4 5 [/SUP], Allison Babb[SUP] 4 5 [/SUP], Michael R Betts[SUP] 1 8 [/SUP], Eline T Luning Prak[SUP] 1 9 [/SUP], Daniela Weiskopf[SUP] 10 [/SUP], Alba Grifoni[SUP] 10 [/SUP], Kendall A Lundgreen[SUP] 8 11 [/SUP], Sigrid Gouma[SUP] 1 8 [/SUP], Alessandro Sette[SUP] 10 12 [/SUP], Paul Bates[SUP] 8 11 [/SUP], Scott E Hensley[SUP] 1 8 [/SUP], Allison R Greenplate[SUP] 1 3 [/SUP], E John Wherry[SUP] 13 14 15 16 [/SUP], Rui Li[SUP] 17 18 [/SUP], Amit Bar-Or[SUP] 19 20 [/SUP]
Affiliations
Abstract
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[SUB]FH[/SUB]) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T[SUB]H[/SUB]1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T[SUB]FH[/SUB] 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.
. 2021 Sep 14.
doi: 10.1038/s41591-021-01507-2. Online ahead of print.
Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy
Sokratis A Apostolidis[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Mihir Kakara[SUP] #[/SUP][SUP] 4 5 [/SUP], Mark M Painter[SUP] #[/SUP][SUP] 1 3 6 [/SUP], Rishi R Goel[SUP] #[/SUP][SUP] 1 3 6 [/SUP], Divij Mathew[SUP] 1 3 6 [/SUP], Kerry Lenzi[SUP] 5 [/SUP], Ayman Rezk[SUP] 4 5 [/SUP], Kristina R Patterson[SUP] 4 5 [/SUP], Diego A Espinoza[SUP] 4 5 7 [/SUP], Jessy C Kadri[SUP] 4 5 [/SUP], Daniel M Markowitz[SUP] 4 5 [/SUP], Clyde E Markowitz[SUP] 4 5 [/SUP], Ina Mexhitaj[SUP] 4 5 [/SUP], Dina Jacobs[SUP] 4 5 [/SUP], Allison Babb[SUP] 4 5 [/SUP], Michael R Betts[SUP] 1 8 [/SUP], Eline T Luning Prak[SUP] 1 9 [/SUP], Daniela Weiskopf[SUP] 10 [/SUP], Alba Grifoni[SUP] 10 [/SUP], Kendall A Lundgreen[SUP] 8 11 [/SUP], Sigrid Gouma[SUP] 1 8 [/SUP], Alessandro Sette[SUP] 10 12 [/SUP], Paul Bates[SUP] 8 11 [/SUP], Scott E Hensley[SUP] 1 8 [/SUP], Allison R Greenplate[SUP] 1 3 [/SUP], E John Wherry[SUP] 13 14 15 16 [/SUP], Rui Li[SUP] 17 18 [/SUP], Amit Bar-Or[SUP] 19 20 [/SUP]
Affiliations
- PMID: 34522051
- DOI: 10.1038/s41591-021-01507-2
Abstract
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[SUB]FH[/SUB]) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T[SUB]H[/SUB]1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T[SUB]FH[/SUB] 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.