scholarly journals Covid-19 vaccine-induced antibodies are attenuated and decay rapidly in infliximab treated patients

2021 ◽  
Author(s):  
Simeng Lin ◽  
Nicholas Kennedy ◽  
Aamir Saifuddin ◽  
Diana Muñoz Sandoval ◽  
Catherine Reynolds ◽  
...  
Keyword(s):  
T Cell ◽  
Tumour Necrosis Factor ◽  
Specific Antibody ◽  
Tumour Necrosis ◽  
Inflammatory Diseases ◽  
T Cell Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Immunosuppressed Patients ◽  
Necrosis Factor

Abstract To inform healthcare policy for immunosuppressed patients there is a need to define SARS-CoV-2 vaccine responses. Here we report SARS-CoV-2 vaccine-induced antibody and T cell responses in patients treated with anti-tumour necrosis factor (anti-TNF), a commonly used biologic in inflammatory diseases, compared to patients treated with vedolizumab, a gut-specific antibody targeting integrin a4b7 that does not impair systemic immunity. In anti-TNF recipients, the magnitude of anti-SARS-CoV2 antibodies was reduced five-fold, and rapidly decayed towards the seroconversion threshold by 14 weeks after second dose of vaccine. In contrast, anti-SARS-CoV-2 antibodies were sustained up to 16 weeks in vedolizumab-treated patients. Anti-SARS-CoV2 antibody decay was not observed in vaccinated patients previously infected with SARS-CoV-2. T cell responses were absent in one-fifth of anti-TNF and vedolizumab-treated patients after a second dose of either vaccine. Our data have important implications for anti-TNF recipients, including the need for vaccine prioritization, booster doses, and social distancing strategies.

scholarly journals Cellular and humoral responses to SARS-CoV-2 vaccination in immunosuppressed patients

2021 ◽  
Author(s):  
Dinesh Mohanraj ◽  
Samuel Baldwin ◽  
Satbeer Singh ◽  
Alun Gordon ◽  
Alison Whitelegg
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Effector Memory ◽  
Immunological Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Immunosuppressed Patients ◽  
Vaccine Immunogenicity ◽  
Humoral Responses ◽  
The Impact

ABSTRACTObjectiveSARS-CoV-2 vaccinations have demonstrated vaccine immunogenicity in healthy volunteers, however, efficacy in immunosuppressed patients is less well characterised. Subsequently, there is an urgent need to address the impact of immunosuppression on vaccine immunogenicity.MethodsSerological, T-cell ELISpot, cytokines and immunophenotyping investigations were used to assess vaccine responses (either BNT162b2 mRNA or ChAdOx1 nCoV-19) in double-vaccinated patients receiving immunosuppression for renal transplants or haematological malignancies (n=13). Immunological responses in immunosuppressed patients (VACC-IS) were compared to immunocompetent vaccinated (VACC-IC, n=12), unvaccinated (UNVACC, n=11) and infection-naïve unvaccinated (HC, n=3) cohorts. All participants, except HC, had prior COVID-19 infection.ResultsT-cell responses were identical between VACC-IS and VACC-IC (92%) to spike-peptide (S) stimulation. UNVACC had the highest T-cell non-responders (n=3), whereas VACC-IC and VACC-IS both had one T-cell non-responder. No significant differences in humoral responses were observed between VACC-IC and VACC-IS, with 92% (12/13) of VACC-IS patients demonstrating seropositivity. One VACC-IS failed to seroconvert, however had detectable T-cell responses. All VACC-IC participants were seropositive for anti-spike antibodies. Furthermore, both VACC-IS and VACC-IC participants elicited strong Th1 cytokine response with immunodominance towards S-peptide. Differences in T-cell immunophenotyping were seen between VACC-IS and VACC-IC, with lower CD8+ activation and T-effector memory phenotype observed in VACC-IS.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppressive therapy, with responses comparable to vaccinated immunocompetent participants. Lower humoral responses were seen in patients treated with B-cell depleting therapeutics, but with preserved T-cell responses. We suggest further work to correlate both protective immunity and longevity of these responses in both healthy and immunosuppressed patients.

scholarly journals Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy.

2021 ◽  
Author(s):  
Sokratis A. Apostolidis ◽  
Mihir Kakara ◽  
Mark M Painter ◽  
Rishi Raj Goel ◽  
Divij Mathew ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Specific Antibody ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Immunosuppressed Patients ◽  
Anti Cd20

SARS-CoV-2 mRNA vaccination in healthy individuals generates effective immune protection against COVID-19. Little is known, however, about the SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses in patients with multiple sclerosis on anti-CD20 (MS-aCD20) monotherapy following SARS-CoV-2 mRNA vaccination. Treatment with aCD20 significantly reduced Spike and RBD specific antibody and memory B cell responses in most patients, an effect that was ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. In contrast, all MS-aCD20 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. However, treatment with aCD20 skewed these responses compromising circulating Tfh responses and augmenting CD8 T cell induction, while largely preserving Th1 priming. These data also revealed underlying features of coordinated immune responses following mRNA vaccination. Specifically, the MS-aCD20 patients who failed to generate anti-RBD IgG had the most severe defect in cTfh cell responses and more robust CD8 T cell responses compared to those who generated anti-RBD IgG, whose T cell responses were more similar to healthy controls. These data define the nature of 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, patient education and public health policy for patients treated with aCD20 and other immunosuppressed patients.

scholarly journals Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

2021 ◽  
Author(s):  
Sokratis A. Apostolidis ◽  
Mihir Kakara ◽  
Mark M. Painter ◽  
Rishi R. Goel ◽  
Divij Mathew ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Specific Antibody ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Immunosuppressed Patients ◽  
Anti Cd20

AbstractSARS-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 (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH 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.

scholarly journals Cellular and Humoral Responses to SARS-CoV-2 Vaccination in Immunosuppressed Patients

2022 ◽  
Author(s):  
Dinesh Mohanraj ◽  
Samuel Baldwin ◽  
Satbeer Singh ◽  
Alun Gordon ◽  
Alison Whitelegg
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Effector Memory ◽  
Immunological Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Immunosuppressed Patients ◽  
Vaccine Immunogenicity ◽  
Humoral Responses ◽  
The Impact

Abstract Objective: SARS-CoV-2 vaccinations have demonstrated vaccine-immunogenicity in healthy volunteers, however, efficacy in immunosuppressed patients is less well characterised. There is an urgent need to address the impact of immunosuppression on vaccine immunogenicity. Methods: Serological, T-cell ELISpot, cytokines and immunophenotyping assays were used to assess vaccine responses (either BNT162b2 mRNA or ChAdOx1 nCoV-19) in double-vaccinated patients receiving immunosuppression for renal transplants or haematological malignancies (n=13). Immunological responses in immunosuppressed patients (VACC-IS) were compared to immunocompetent vaccinated (VACC-IC, n=12), unvaccinated (UNVACC, n=11) and infection-naïve unvaccinated (HC, n=3) cohorts. All participants, except HC, had prior COVID-19 infection. Results: T-cell responses were identical between VACC-IS and VACC-IC (92%) to spike-peptide (S) stimulation. UNVACC had the highest T-cell non-responders (n=3), whereas VACC-IC and VACC-IS both had one T-cell non-responder. No significant differences in humoral responses were observed between VACC-IC and VACC-IS, with 92% (12/13) of VACC-IS patients demonstrating seropositivity. One VACC-IS failed to seroconvert, however had detectable T-cell responses. All VACC-IC participants were seropositive for anti-spike antibodies. VACC-IS and VACC-IC participants elicited strong Th1 cytokine response with immunodominance towards S-peptide. Differences in T-cell immunophenotyping were seen between VACC-IS and VACC-IC, with lower CD8+ activation and T-effector memory phenotype observed in VACC-IS. Conclusion: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppressive therapy, with responses comparable to vaccinated immunocompetent participants. Lower humoral responses were seen in patients treated with B-cell depleting therapeutics, but with preserved T-cell responses. We suggest further work to correlate both protective immunity and longevity of these responses in both healthy and immunosuppressed patients.

scholarly journals TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand–independent T Helper Cell Activation

1999 ◽  
Vol 189 (7) ◽  
pp. 1025-1031 ◽  
Author(s):  
Martin F. Bachmann ◽  
Brian R. Wong ◽  
Régis Josien ◽  
Ralph M. Steinman ◽  
Annette Oxenius ◽  
...  
Keyword(s):  
T Cell ◽  
Family Member ◽  
T Cell Responses ◽  
Cd40 Ligand ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
T Cell Priming ◽  
Deficient Mice ◽  
Necrosis Factor

CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4+ T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4+ T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4+ T cell responses that produce normal levels of interferon γ, suggesting a CD40L/CD40-independent mechanism of CD4+ T cell priming that to date has not been elucidated. Here we show that CD4+ T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4+ T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4+ T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention.

Selective down-regulation of T cell- and non-T cell-derived tumour necrosis factor α by thalidomide: comparisons with dexamethasone

1999 ◽  
Vol 68 (2-3) ◽  
pp. 325-332 ◽  
Author(s):  
Tom L Rowland ◽  
Simon M McHugh ◽  
John Deighton ◽  
Pamela W Ewan ◽  
Rebecca J Dearman ◽  
...  
Keyword(s):  
T Cell ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Down Regulation ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Interleukin-1, Tumour Necrosis Factor and Treatment of the Septic Shock Syndrome

1992 ◽  
Vol 3 (suppl b) ◽  
pp. 11-19
Author(s):  
Charles A Dinarello
Keyword(s):  
Septic Shock ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Neutralizing Antibodies ◽  
Inflammatory Diseases ◽  
Leukocyte Adhesion ◽  
Interleukin 1 ◽  
Platelet Activating Factor ◽  
Surface Receptors ◽  
Necrosis Factor

Treating the septic shock syndrome with antibodies that block only endotoxin has its limitations. Other targets for treating septic shock include neutralizing antibodies to the complement fragment C5a, platelet activating factor antagonists and blockade of endothelial cell leukocyte adhesion molecules. Specific blockade of the pro-inflammatory cytokines interleukin-1 (IL-1) or tumour necrosis factor (TNF) reduces the morbidity and mortality associated with septic shock. Moreover, blocking IL-1 and TNF likely has uses in treating diseases other than septic shock. Use of neutralizing antibodies to TNF or IL-1 receptors has reduced the consequences of infection and inflammation, including lethal outcomes in animal models. The IL-1 receptor antagonist, a naturally occurring cytokine, blocks shock and death due to Escherichia coli as well as ameliorates a variety of inflammatory diseases. Soluble TNF and IL-1 surface receptors, which bind their respective cytokines. also ameliorate disease processes. Clinical trials are presently evaluating the safety and efficacy of anticytokine therapies either alone or in combination.

Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice

Nature ◽  
1994 ◽  
Vol 372 (6506) ◽  
pp. 560-563 ◽  
Author(s):  
Sharon L. Erickson ◽  
Frederic J. de Sauvage ◽  
Kristine Kikly ◽  
Karen Carver-Moore ◽  
Sharon Pitts-Meek ◽  
...  
Keyword(s):  
T Cell ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
T Cell Development ◽  
Cell Development ◽  
Tnf Receptor ◽  
Deficient Mice ◽  
Necrosis Factor

scholarly journals CD4+ Tissue-resident Memory T Cells Expand and Are a Major Source of Mucosal Tumour Necrosis Factor α in Active Crohn’s Disease

2019 ◽  
Vol 13 (7) ◽  
pp. 905-915 ◽  
Author(s):  
Shrinivas Bishu ◽  
Mohammed El Zaatari ◽  
Atsushi Hayashi ◽  
Guoqing Hou ◽  
Nicole Bowers ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Ex Vivo ◽  
Factor Α ◽  
And Control ◽  
Necrosis Factor

Abstract Background and Aims Tumour necrosis factor [TNF]α- and IL-17A-producing T cells are implicated in Crohn’s disease [CD]. Tissue-resident memory T [TRM] cells are tissue-restricted T cells that are regulated by PR zinc finger domain 1 [PRDM1], which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defence but their role in CD is unknown. We thus examined CD4+ TRM cells in CD. Methods Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterise CD4+ TRM cells. Results CD4+ TRM cells are the most abundant memory T cell population and are the major T cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD which are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells Conclusions CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting that they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.

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