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Frontiers in Immunology 2024The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype...
The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline versions of VH6-1 antibodies, use these to sort human leukocytes, and isolate a new VH6-1-class member, antibody L5A7, which potently neutralized diverse group 1 and group 2 influenza A strains. While its heavy chain derived from the canonical IGHV6-1 heavy chain gene used by the class, L5A7 utilized a light chain gene, IGKV1-9, which had not been previously observed in other VH6-1-class antibodies. The cryo-EM structure of L5A7 in complex with Indonesia 2005 hemagglutinin revealed a nearly identical binding mode to other VH6-1-class members. The structure of L5A7 bound to the isolating anti-idiotype antibody, 28H6E11, revealed a shared surface for binding anti-idiotype and hemagglutinin that included two critical L5A7 regions: an FG motif in the third heavy chain-complementary determining region (CDR H3) and the CDR L1 loop. Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen.
Topics: Humans; Influenza A virus; Antibodies, Viral; Antibodies, Neutralizing; Antibodies, Anti-Idiotypic; Hemagglutinin Glycoproteins, Influenza Virus; Influenza, Human; Animals; Immunoglobulin Heavy Chains
PubMed: 38873606
DOI: 10.3389/fimmu.2024.1399960 -
Talanta Jun 2024We developed an aptamer-based fluorescence resonance energy transfer (FRET) assay capable of recognizing therapeutic monoclonal antibody bevacizumab and rapidly...
We developed an aptamer-based fluorescence resonance energy transfer (FRET) assay capable of recognizing therapeutic monoclonal antibody bevacizumab and rapidly quantifying its concentration with just one mixing step. In this assay, two fluorescent dyes (fluorescein and tetramethylrhodamine) labeled aptamers bind to two Fab regions on bevacizumab, and FRET fluorescence is observed when both dyes come into close proximity. We optimized this assay in three different formats, catering to a wide range of analytical needs. When applied to hybridoma culture samples in practical settings, this assay exhibited a signal response that was concentration-dependent, falling within the range of 50-2000 μg/mL. The coefficients of determination (r) ranged from 0.998 to 0.999, and bias and precision results were within ±24.0 % and 20.3 %, respectively. Additionally, during thermal and UV stress testing, this assay demonstrated the ability to detect denatured samples in a manner comparable to conventional Size Exclusion Chromatography. Notably, it offers the added advantage of detecting decreases in binding activity without changes in molecular weight. In contrast to many existing process analytical technology tools, this assay not only identifies bevacizumab but also directly measures the quality attributes related to mAb efficacy, such as the binding activity. As a result, this assay holds great potential as a valuable platform for providing highly reliable quality attribute information in real-time. We consider this will make a significant contribution to the worldwide distribution of high-quality therapeutic mAbs in various aspects of antibody manufacturing, including production monitoring, quality control, commercial lot release, and stability testing.
PubMed: 38852342
DOI: 10.1016/j.talanta.2024.126349 -
Current Opinion in Allergy and Clinical... Aug 2024To acknowledge, the newly available treatments for food allergy described in the latest scientific literature, such as oral immunotherapy (OIT), biologics and the... (Review)
Review
PURPOSE OF REVIEW
To acknowledge, the newly available treatments for food allergy described in the latest scientific literature, such as oral immunotherapy (OIT), biologics and the combination of them in managing patients with IgE-mediated food allergies.
RECENT FINDINGS
Recent studies suggest that OIT and biologics, alone or together, can have a role as disease-modifying treatments for food allergies. The FDA has recently approved omalizumab as a treatment for food allergy. Other biologics are currently under evaluation and further studies are needed to assess the efficacy and safety of these therapies.
SUMMARY
The allergology scenario is rapidly evolving, the recent introduction and approval of new therapeutic strategies such as biotechnological drugs and allergen immunotherapy is changing the therapeutic paradigm: we are witnessing a shift from a strategy based on avoiding the trigger and reversing an allergic reaction already in progress, to one that aims to modify the natural history of the disease by acting on the immunological mechanisms that determine it. This approach is consistent with the modern perspective of a personalized patient-tailored medicine. In this opinion review, we will provide a brief analysis of current and future therapeutic options for IgE-mediated food allergy, focusing on OIT, biologics and their combination.
Topics: Humans; Food Hypersensitivity; Desensitization, Immunologic; Omalizumab; Immunoglobulin E; Biological Products; Allergens; Animals; Anti-Allergic Agents; Administration, Oral; Precision Medicine
PubMed: 38814736
DOI: 10.1097/ACI.0000000000000999 -
The New England Journal of Medicine May 2024
Topics: Humans; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Food Hypersensitivity; Immunoglobulin E; Omalizumab; Adult
PubMed: 38810198
DOI: 10.1056/NEJMc2404288 -
The New England Journal of Medicine May 2024
Topics: Child; Humans; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Food Hypersensitivity; Immunoglobulin E; Omalizumab; Adult
PubMed: 38810197
DOI: 10.1056/NEJMc2404288 -
Archives of Dermatological Research May 2024While several studies have examined the role of T cells and related cytokines in the development of chronic spontaneous urticaria (CSU), there is a limited amount of...
While several studies have examined the role of T cells and related cytokines in the development of chronic spontaneous urticaria (CSU), there is a limited amount of research focusing on the changes in cytokine levels during omalizumab treatment. The primary objective of this study was to investigate the inflammatory cytokine profile (including IL-4, IL-5, IL-10, IL-13, IL-17, IL-31, IL-33, and TNFα) among CSU patients undergoing to omalizumab treatment. Plasma levels of cytokines were measured using ELISA. Measurements were taken before CSU treatment, at the 3rd and 6th months of omalizumab treatment, and once in the control group. The severity of the patients' disease was assessed using the weekly Urticaria Activity Score(UAS7), and disease control was evaluated using the Urticaria Control Test(UCT). Thirty-one CSU patients and 56 age- and gender-matched healthy controls were included. Plasma levels of IL-4 and IL-33 were significantly lower in patients with CSU compared to healthy controls (p = 0.001; p = 0.038, respectively). During omalizumab treatment, IL-4 levels showed a significant increase in the 3rd month compared to baseline (p = 0.01), and IL-5 levels significantly decreased in the 6th month compared to both the 3rd month and baseline (6th month vs. baseline; p = 0.006, 6th month vs. 3rd month; p = 0.001). One potential mechanism of action for omalizumab may involve its regulatory effects on type 2 inflammatory cytokines in CSU patients. This finding partially explains the efficacy of anti-IL-4/13 treatments in chronic spontaneous urticaria. Further investigations on drugs targeting type 2 inflammatory cytokines in CSU are warranted.
Topics: Humans; Omalizumab; Female; Male; Adult; Chronic Urticaria; Middle Aged; Cytokines; Anti-Allergic Agents; Severity of Illness Index; Treatment Outcome; Case-Control Studies; Young Adult
PubMed: 38795119
DOI: 10.1007/s00403-024-02966-6 -
Medicina (Kaunas, Lithuania) Apr 2024The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the... (Observational Study)
Observational Study
The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the effectiveness of anti-H1, omalizumab, montelukast, and systemic glucocorticoids is rarely reported in the pediatric population. There is a wide variation in the rate of remission of chronic urticaria between studies. The aim of this study is to enhance our understanding of pediatric chronic urticaria. This study enrolled 37 children with chronic urticaria aged from 0 to 18 years. Demographic parameters, medical history, clinical features, laboratory data and treatment information were collected. Children were treated with the recommended dosage of second-generation H1-antihistamines, which was increased by up to twofold. Omalizumab was added for refractory anti-H1 patients. A three-day course with systemic glucocorticoids was administered for severe exacerbations. Montelukast was administered to some children. : Wheals without angioedema were common. Chronic urticaria was spontaneous in 32 children (86.48%), inducible in 2 (5.41%), induced by a parasite in 1 and vasculitic in 2. Treatment of the potential causes of chronic urticaria was of no benefit, except for eradication of Dientamoeba fragilis. Chronic urticaria was resolved within three years in 45.9% of cases. Allergic diseases were present in nine children (24.32%) and autoimmune diseases were present in three (8.11%). All children were treated with anti-H1 at the licensed dose or at a higher dose. A partial or complete response to anti-H1 was observed in 29 (78.38%) patients. Montelukast showed no benefit. All children treated with omalizumab responded. Systemic glucocorticoids were successfully used to treat exacerbations. Our findings indicate that laboratory tests should not be routinely performed in children with chronic urticaria without clinical suspicion. However, comorbidities such as thyroid autoimmune disease and coeliac disease are suggested to be monitored over the chronic urticaria course. These clinical conditions could be diagnosed from the diagnostic framework of chronic urticaria. Increasing the dosage of anti-H1 and omalizumab was effective in children resistant to standard treatment but we still need further studies to generate a standard patient-centered treatment.
Topics: Humans; Child; Female; Male; Child, Preschool; Adolescent; Chronic Urticaria; Infant; Sulfides; Cyclopropanes; Quinolines; Acetates; Omalizumab; Histamine H1 Antagonists; Glucocorticoids; Anti-Allergic Agents; Infant, Newborn; Chronic Disease; Urticaria
PubMed: 38792886
DOI: 10.3390/medicina60050704 -
Terapevticheskii Arkhiv Jan 2024This article presents the experience of successfully switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml in a patient with a combined allergic and...
This article presents the experience of successfully switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml in a patient with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. The effectiveness of biological therapy was evaluated when switching from omalizumab 150 mg subcutaneously at a dose of 600 mg for 36 weeks. Therapy for the drug benralizumab 30 mg/1 ml subcutaneously the first three injections monthly, the rest a month later for 52 weeks with bronchial asthma (BA), a severe uncontrolled course with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs in a patient Ch., born in 2004. Switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml allowed to achieve complete control of asthma symptoms (AST = 23 points), to achieve the absence of asthma exacerbations during 52 weeks, restore respiratory function to normal values, as well as improve the quality of life. The study reflects the good tolerability, high efficacy and safety of biological therapy when switching from one genetically engineered biological drug (GIBP) omalizumab 150 mg to another GIBP benralizumab 30 mg/1 ml in severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. Therapy with benralizumab 30 mg/1 ml in severe BA has demonstrated a more effective clinically significant improvement in the course of the disease, control of symptoms of the disease. Reduction of exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. Consequently, the use of different biological molecules for the therapy of BA with a combined allergic and eosinophilic phenotype contributes to achieving disease control, improving the patient's quality of life and reducing the dose of oral glucocorticosteroids. The targeted biological drug benralizumab 30 mg/1 ml has a targeted effect on the key links in the pathogenesis of severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs and reduces the burden of severe disease.
Topics: Humans; Asthma; Antibodies, Monoclonal, Humanized; Omalizumab; Anti-Asthmatic Agents; Treatment Outcome; Female; Drug Substitution; Quality of Life
PubMed: 38785050
DOI: 10.26442/00403660.2023.12.202491 -
Skin Research and Technology : Official... May 2024Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial.... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.
MATERIALS AND METHODS
Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta-analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk-of-bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs).
RESULTS
In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta-regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo.
CONCLUSION
300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.
Topics: Omalizumab; Humans; Chronic Urticaria; Anti-Allergic Agents; Treatment Outcome; Network Meta-Analysis; Randomized Controlled Trials as Topic; Quality of Life; Dose-Response Relationship, Drug
PubMed: 38776128
DOI: 10.1111/srt.13749 -
Journal of Inflammation Research 2024Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in...
PURPOSE
Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.
METHODS
This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10, IFN-γ and FoxP3CD4T cells in murine spleen.
RESULTS
It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3, IL-10 and IFN-γ CD4T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.
CONCLUSION
These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.
PubMed: 38751687
DOI: 10.2147/JIR.S454325