scholarly journals Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease

2021 ◽  
Author(s):  
Rebecca H Haberman ◽  
Ramin Herati ◽  
David Simon ◽  
Marie Samanovic ◽  
Rebecca B. Blank ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell Activation ◽  
Cellular Immune Response ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Inflammatory Diseases ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Immune Mediated ◽  
Cellular Immune

Objective: To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods: Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results: Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions: In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

scholarly journals Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

2020 ◽  
Author(s):  
Nina Le Bert ◽  
Hannah E Clapham ◽  
Anthony T Tan ◽  
Wan Ni Chia ◽  
Christine YL Tham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Inflammatory Cytokines ◽  
T Cell Activation ◽  
Cellular Immune Response ◽  
Cell Activation ◽  
Tnf Α ◽  
Specific Cellular Immune Response ◽  
Ifn Γ ◽  
Cellular Immune

AbstractThe efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-γ, IL-4, IL-6, IL-1β, TNF-α and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-γ and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.

scholarly journals Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

2021 ◽  
Vol 218 (5) ◽  
Author(s):  
Nina Le Bert ◽  
Hannah E. Clapham ◽  
Anthony T. Tan ◽  
Wan Ni Chia ◽  
Christine Y.L. Tham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell Activation ◽  
Cellular Immune Response ◽  
Cell Activation ◽  
Asymptomatic Infection ◽  
Tnf Α ◽  
Specific Cellular Immune Response ◽  
Ifn Γ ◽  
Cellular Immune

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.

Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation

2006 ◽  
Vol 55 (12) ◽  
pp. 1459-1469 ◽  
Author(s):  
Yohei Kida ◽  
Sachiyo Tsuji-Kawahara ◽  
Valentina Ostapenko ◽  
Saori Kinoshita ◽  
Eiji Kajiwara ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
T Cell Activation ◽  
Cellular Immune Response ◽  
Cell Activation ◽  
Cellular Immune

HIV-infected patients show impaired cellular immune response to influenza vaccination compared to healthy subjects

Vaccine ◽  
2013 ◽  
Vol 31 (28) ◽  
pp. 2914-2918 ◽  
Author(s):  
Massimiliano Fabbiani ◽  
Letizia Sidella ◽  
Maddalena Corbi ◽  
Rosa Martucci ◽  
Michela Sali ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Vaccination ◽  
Cellular Immune Response ◽  
Healthy Subjects ◽  
Cellular Immune

A randomized phase II study evaluating the optimal sequencing of sipuleucel-T and androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC): Immune results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5016-5016 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Adam S Kibel ◽  
George Adams ◽  
Lawrence Ivan Karsh ◽  
Aymen Elfiky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Preliminary Data ◽  
Cellular Immune Response ◽  
Cell Activity ◽  
Optimal Sequencing ◽  
Cellular Immune

5016 Background: ADT is a standard treatment for men with BRPC after failure of local therapy, and has immunomodulatory effects. Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic/minimally symptomatic metastatic castrate resistant prostate cancer. The STAND trial (NCT01431391) aimed to evaluate optimal sequencing of sipuleucel-T and ADT in men with BRPC at high risk for metastases (ie PSA doubling time ≤12 mo). Methods: Men were randomized (1:1) to Arm 1: sipuleucel-T followed by ADT (2 wks after 3rd infusion); or Arm 2: ADT (3 mo lead in) followed by sipuleucel-T. All men had 3 doses of sipuleucel-T and 12 mo of ADT (45 mg leuprolide SQ at 6 mo intervals). The primary endpoint is cellular immune response (ELISPOT to PA2024 [PAP-GMCSF]). Secondary endpoints are humoral and cytokine responses, product parameters and safety. Results: 68 men were randomized. Preliminary data show higher levels of serum cytokines in Arm 2 vs Arm 1, with a pattern suggesting a mixed TH1/TH2 cellular immune response; elevations were seen in TH1 (IFNγ, IL 12), TH2 (IL 4, 5, 10, 13) and TH17 (IL 17) subsets (all P<.05). The increase in TH1 cytokines was consistent with a trend toward higher PA2024-specific ELISPOT responses 2 wk after the 3rd sipuleucel-T infusion in Arm 2 vs Arm 1 (40.5 vs 12.8 spots; P=.086), suggesting increased T cell activation in Arm 2. Antigen-specific humoral responses were induced in both arms with no differences yet observed between arms. Sipuleucel-T product parameters were roughly equivalent in both arms with APC activation data indicating a robust prime-boost effect. Conclusions: While confirmation is required, these preliminary data suggest that tumor-specific T cell responses and broad based immune responses are augmented when sipuleucel-T is given after rather than before ADT initiation. These data are consistent with preclinical studies showing that ADT enhances T cell activity, and provide preliminary evidence that combining ADT with sipuleucel-T may augment adaptive immunity. Further follow up will determine whether augmented immune responses correlate with clinical parameters (eg PSA recurrence). Clinical trial information: NCT01431391.

scholarly journals Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shidan Tosif ◽  
Melanie R. Neeland ◽  
Philip Sutton ◽  
Paul V. Licciardi ◽  
Sohinee Sarkar ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Family Members ◽  
Antibody Responses ◽  
Healthy Controls ◽  
Serological Testing ◽  
Igg Antibody ◽  
Cytokine Responses ◽  
Asymptomatic Infections ◽  
Cellular Immune

Abstract Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

scholarly journals Immune Modulatory Effects of Hypercholesterolemia: Can Atorvastatin Convert the Detrimental Effect of Hypercholesterolemia on the Immune System?

2019 ◽  
Author(s):  
Zeinab Emruzi ◽  
Pegah Babaheidarian ◽  
Mahmoud Arshad ◽  
Hannes Stockinger ◽  
Ghasem Ahangari
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell Activation ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Detrimental Effect ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Gene And Protein Expression ◽  
Treatment Naïve

Many observations showed that hypercholesterolemia can disrupt immune response. Statin drugs that were used for the treatment of hypercholesterolemia patients can interfere in the regulation of the immune response and cytokine secretion. The primary aim of the current study was to investigate the immune response among treatment-naïve patients with hypercholesterolemia and healthy subjects. The secondary goal of the study was to determine whether atorvastatin can reverse the detrimental effect of hypercholesterolemia on the immune system. Peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients afflicted with hypercholesterolemia who were treatment-naïve along with 50 sex/age-matched hypercholesterolemia patients receiving atorvastatin, and 50 sex/age-matched healthy subjects. Quantitative PCR and ELISA methods were used for gene and protein expression analysis of T helper 1 (Th1) and Th2 related cytokines. Additionally, the expression of the cluster of differentiation (CD) markers on T, B, and natural killer (NK) cells was measured by flow cytometry method. The results showed that hypercholesterolemia and atorvastatin down-regulated the expression of Th1-related cytokines and elevated the levels of Th2-related cytokines. The expression of cell surface markers, CD25 and CD69, was significantly decreased in the treatment-naïve, and atorvastatin groups. It seems that atorvastatin is not able to repair the deleterious effects of hypercholesterolemia on the immune system. Moreover, elevated levels of cholesterol along with the administration of atorvastatin tilt the Th1/Th2 balance in favor of Th2 and reduce T cell activation.

APPROACHES TO THE ESTIMATION OF SOME PARAMETERS OF HUMORAL AND CELLULAR IMMUNE RESPONSE TO BACTERIOPHAGES

2019 ◽  
Vol 64 (4) ◽  
pp. 237-242 ◽  
Author(s):  
Svetlana Sergeevna Bochkareva ◽  
A. V. Karaulov ◽  
A. V. Aleshkin ◽  
I. I. Novikova ◽  
I. M. Fedorova ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Cellular Immune Response ◽  
Phage Therapy ◽  
Elisa Test ◽  
Cytotoxic Lymphocytes ◽  
Igg Antibody ◽  
Cell Immunity ◽  
Activated T Lymphocytes ◽  
Cellular Immune

The aim of the study was to develop some approaches to evaluate the basic parameters of the humoral and cellular immune response to a bacteriophage, taking into account the multifactorial aspects of its interaction with both the pathogen and the macroorganism. The necessary reagents were obtained and a line of diagnostic ELISA test systems was designed to allow semi-quantitative assessment of the anti-bacteriophage IgG-antibody level in serum or other biological human fluids, as well as in preparations obtained from human blood. The need for neutralization reaction to determine the effect of detected antibodies on phage activity against a target bacterium has been proven. Testing the approaches used in the investigation of patients’ blood sera showed that antibodies to bacteriophages synthesized during phage therapy are not always neutralizing. Also approaches have been developed to evaluate cell immunity reactions to bacteriophage namely to identify T-lymphocytes (T-helpers and cytotoxic lymphocytes) that can be activated in the presence of the phage under study (by expressing the early activation marker (CD69) and by the ability to produce IFNγ). Approbation of the technique in the study of lymphocytes in patients during phage therapy showed the presence of activated cells by both the CD69 expression and IFNγ production, the dynamics of which depended on the timing and frequency of therapy. The appearance of neutralizing anti-phage antibodies and corresponding activated T-lymphocytes should be taken into account in phage therapy, the effectiveness of which can directly depend not only on the activity of the phage against the target bacterium, but also on the response of the patient’s immune system to the bacteriophage.

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