Humoral immune responses against Wilms tumor gene WT1product in patients with hematopoietic malignancies

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3272-3279 ◽  
Author(s):  
Olga A. Elisseeva ◽  
Yoshihiro Oka ◽  
Akihiro Tsuboi ◽  
Kiyoyuki Ogata ◽  
Fei Wu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Immunoglobulin Isotype ◽  
Hematopoietic Malignancies ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Wt1 Protein ◽  
Tumor Gene

Abstract Wilms tumor gene WT1 is expressed at high levels in hematopoietic malignancies, such as leukemias and myelodysplastic syndromes (MDS), and in various kinds of solid tumors, including lung cancer, and it exerts an oncogenic function in these malignancies. IgM and IgG WT1 antibodies were measured by means of dot blot assay in 73 patients with hematopoietic malignancies (16 acute myeloid leukemia [AML], 11 acute lymphoid leukemia [ALL], 13 chronic myeloid leukemia [CML], and 33 MDS) and 43 healthy volunteers. Immunoglobulin IgM, IgG, and IgM+IgG WT1 antibodies were detected in 40 (54.8%), 40 (54.8%), and 24 (32.8%), respectively, of the 73 patients with hematopoietic malignancies, whereas 7 (16.2%), 2 (4.7%), and none of the 43 healthy volunteers had IgM, IgG, or IgM+IgG WT1 antibodies, respectively. Furthermore, immunoglobulin isotype class switching of WT1 antibodies from IgM to IgG occurred in conjunction with disease progression from refractory anemia (RA) to RA with excess of blasts (RAEB), and further to RAEB in transformation (RAEB-t) in MDS patients. These results showed that humoral immune responses against the WT1 protein could be elicited in patients with WT1-expressing hematopoietic malignancies, and they suggested that the helper T-cell responses needed to induce humoral immune responses and immunoglobulin isotype class switching from IgM to IgG were also generated in these patients. Our findings may provide new insight into the rationale for elicitation of cytotoxic T-cell responses against the WT1 protein in cancer immunotherapy using the WT1 vaccine.

scholarly journals How to induce protective humoral immunity against Plasmodium falciparum circumsporozoite protein

2022 ◽  
Vol 219 (2) ◽  
Author(s):  
Ilka Wahl ◽  
Hedda Wardemann
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Vaccine Efficacy ◽  
Circumsporozoite Protein ◽  
Surface Proteins ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The induction of protective humoral immune responses against sporozoite surface proteins of the human parasite Plasmodium falciparum (Pf) is a prime goal in the development of a preerythrocytic malaria vaccine. The most promising antibody target is circumsporozoite protein (CSP). Although PfCSP induces strong humoral immune responses upon vaccination, vaccine efficacy is overall limited and not durable. Here, we review recent efforts to gain a better molecular and cellular understanding of anti-PfCSP B cell responses in humans and discuss ways to overcome limitations in the induction of stable titers of high-affinity antibodies that might help to increase vaccine efficacy and promote long-lived protection.

scholarly journals Characterization of several leukemia-associated antigens inducing humoral immune responses in acute and chronic myeloid leukemia

2003 ◽  
Vol 106 (2) ◽  
pp. 224-231 ◽  
Author(s):  
Jochen Greiner ◽  
Mark Ringhoffer ◽  
Masanori Taniguchi ◽  
Thomas Hauser ◽  
Anita Schmitt ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Immune Responses ◽  
Myeloid Leukemia ◽  
Humoral Immune ◽  
Humoral Immune Responses

EBV-specific immune responses in patients with multiple sclerosis responding to IFNβ therapy

2011 ◽  
Vol 18 (5) ◽  
pp. 605-609 ◽  
Author(s):  
Manuel Comabella ◽  
Kristina Kakalacheva ◽  
Jordi Río ◽  
Christian Münz ◽  
Xavier Montalban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Lytic Replication ◽  
Nuclear Antigen ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Specific Igg

Background: Symptomatic primary infection with the human γ-herpesvirus Epstein–Barr virus (EBV) and elevated immune responses to EBV are associated with the development and progression of multiple sclerosis (MS). Interferon-beta (IFNβ), first-line treatment for relapse-onset MS, exhibits complex immunoregulatory and antiviral activities. Objective: To determine EBV-specific immune responses in patients with MS during IFNβ therapy. Methods: We evaluated cellular and humoral immune responses to EBV- and human cytomegalovirus (HCMV)-encoded antigens in patients with MS before and 1 year after IFNβ treatment by ELISA and flow cytometry. Twenty-eight patients with MS who showed a clinical response to IFNβ as defined by the absence of relapses and lack of progression on the Expanded Disability Status Scale score during the first 2 years of treatment were included. Results: Clinically effective IFNβ-therapy was associated with a downregulation of proliferative T cell responses to the latent EBV nuclear antigen-1 (EBNA1). EBNA1-specific IgG responses as well as cellular and humoral immune responses to MHC class I restricted EBV antigens expressed during lytic replication and viral B cell transformation were similar before and after IFNβ therapy. Although HCMV-specific IgG levels slightly decreased, proliferative T-cell responses towards HCMV antigens remained unchanged during IFNβ therapy. Conclusion: Clinically effective IFNβ therapy is associated with a reduction of proliferative T-cell responses to EBNA1.

scholarly journals Strong anti-viral responses in pediatric COVID-19 patients in South Brazil

2021 ◽  
Author(s):  
Tiago Fazolo ◽  
Karina Lima ◽  
Julia C. Fontoura ◽  
Priscila Oliveira de Souza ◽  
Gabriel Hilario ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Hla Dr ◽  
Data Points ◽  
Viral Responses ◽  
Immune Profiling

AbstractEpidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children’s T cell responses differed from adults in that their CD8+ TNFα+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.

scholarly journals 479 A lymph-node targeted amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A513-A513
Author(s):  
Martin Steinbuck ◽  
Peter DeMuth ◽  
Lochana Seenappa ◽  
Christopher Haqq ◽  
Aniela Jakubowski ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Receptor Binding ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses

BackgroundThe SARS-CoV-2 pandemic’s public health, economic, and social impacts mandate urgent development of effective vaccines to contain or eradicate infection. To that end, we evaluated a novel amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain (Spike RBD) protein for immunization (ELI 005) in two mouse models. AMP immunogens are efficiently delivered to lymph nodes, where innate and adaptive immune responses are generated.MethodsFemale, 6 to 8-week-old C57BL/6J and BALB/c mice and 37-week-old C57BL/6J mice received two or more doses of benchmark (alum or CpG) or AMP-modified vaccines, comprised of Spike RBD protein and AMP-CpG adjuvant, subcutaneously injected into the tail base in two-week intervals. Antigen was dose spared to determine if AMP-CpG would maintain the immune response. Cellular immune responses were determined via ELISpot analysis of IFNγ production by splenocytes, intracellular cytokine staining of peripheral blood and lung-resident T-cells, and flowcytometric bead array analysis of Th1/2/17 cytokines. Humoral immune responses were determined via blood serum ELISAs to determine sera antibody binding titers, and pseudoviral neutralization assays for comparison to human convalescent serum.ResultsCompared to alum, AMP immunization induced 29-fold higher antigen-specific T cells which produced multiple Th1 cytokines and trafficked into lung parenchyma. Antibody responses favored Th1 isotypes (IgG2bc, IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers >100-fold higher than the natural immune response from convalescent COVID-19 patients; responses were maintained despite 10-fold dose-reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice.ConclusionsELI-005 exhibits the qualities of an optimal SARS-CoV-2 vaccine, which should (1) induce robust and durable CD8+ and CD4+ T cell responses, (2) elicit high magnitude neutralizing antibodies, (3) produce Th1 bias in the elicited antibody and T cell responses, (4) potentially expand pre-existing cross-reactive T cells, (5) enable dose-sparing of required immunogens to improve the speed and cost of broad vaccination campaigns, and (6) be efficacious in elderly populations. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

scholarly journals Strong specific anti-viral responses in pediatric COVID-19 patients in South Brazil

2021 ◽  
Author(s):  
Tiago Fazolo ◽  
Karina Lima ◽  
Julia Fontoura ◽  
Priscila de Souza ◽  
Gabriel Hilario ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Hla Dr ◽  
Data Points ◽  
Viral Responses ◽  
Immune Profiling

Abstract Epidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children’s T cell responses differed from adults in that their CD8+ TNFα+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.

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