-
Annals of Allergy, Asthma & Immunology... Jul 2023Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with... (Review)
Review
Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with mucosal inflammation in asthma. In recent years, the advent of biologics and antialarmins has transformed severe asthma treatment in terms of reducing oral-corticosteroid-requiring exacerbations and improving disease control, asthma quality of life, and spirometry-measured lung function. In contrast, there have been comparatively fewer studies investigating the efficacy of biologics in airway hyperresponsiveness. In this focused review, we summarize the existing evidence base in this area regarding omalizumab, mepolizumab, benralizumab, and tezepelumab.
Topics: Humans; Anti-Asthmatic Agents; Quality of Life; Asthma; Omalizumab; Biological Therapy; Biological Products
PubMed: 36841374
DOI: 10.1016/j.anai.2023.02.016 -
Virologica Sinica Oct 2023Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in...
Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
Topics: Adult; Humans; COVID-19 Vaccines; SARS-CoV-2; Cross-Sectional Studies; COVID-19; Liver Diseases; Antibodies, Viral; Antibodies, Neutralizing; Immunity; Antibodies, Anti-Idiotypic; Immunoglobulin G
PubMed: 37487943
DOI: 10.1016/j.virs.2023.07.005 -
Immunology and Allergy Clinics of North... May 2021Food allergy is a significant public health burden affecting around 10% of adults and 8% of children. Although the first peanut oral immunotherapy product received Food... (Review)
Review
Food allergy is a significant public health burden affecting around 10% of adults and 8% of children. Although the first peanut oral immunotherapy product received Food and Drug Administration approval in 2020, there is still an unmet need for more effective therapeutic options that minimize the risk of anaphylaxis, nutritional deficiencies, and patient's quality of life. Biologics are promising modalities, as they may improve compliance, target multiple food allergies, and treat other concomitant atopic diseases. Although omalizumab has been evaluated extensively, most biologics are more novel and have broader immunologic impact. Careful evaluation of their safety profile should therefore be conducted.
Topics: Allergens; Biological Products; Child; Food Hypersensitivity; Humans; Omalizumab; Quality of Life
PubMed: 33863483
DOI: 10.1016/j.iac.2021.01.002 -
The Cochrane Database of Systematic... Sep 2021Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.
OBJECTIVES
To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.
MAIN RESULTS
Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.
AUTHORS' CONCLUSIONS
There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.
Topics: Antibodies, Anti-Idiotypic; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Humans; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 34550603
DOI: 10.1002/14651858.CD010288.pub5 -
Current Opinion in Allergy and Clinical... Oct 2023The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU). (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU).
RECENT FINDINGS
Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors.
SUMMARY
Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU.
Topics: Humans; Autoimmunity; Urticaria; Chronic Disease; Chronic Urticaria; Autoimmune Diseases; Autoantibodies; Omalizumab
PubMed: 37459281
DOI: 10.1097/ACI.0000000000000927 -
Journal of Immunological Methods Apr 2020The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop...
The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop these molecules for clinical use in the prevention and treatment of HIV-1 infection. As with any protein therapeutic drug product, it is imperative to have qualified assays that can accurately detect and quantify anti-drug antibodies (ADA) that may develop in patients receiving passive administration of HIV-1 bnAbs. Here, we have optimized and qualified a functional assay to assess the potential of ADA to inhibit the neutralizing function of HIV-1 bnAbs. Using a modified version of the validated TZM-bl HIV-1 neutralization assay, murine anti-idiotype antibodies were utilized to optimize and evaluate parameters of linearity, range, limit of detection, specificity, and precision for measuring inhibitory ADA activity against multiple HIV-1 bnAbs that are in clinical development. We further demonstrate the utility of this assay for detecting naturally occurring ADA responses in non-human primates receiving passive administration of human bnAbs. This functional assay format complements binding-antibody ADA strategies being developed for HIV-1 bnAbs, and when utilized together, will support a multi-tiered approach for ADA testing that is compliant with Good Clinical Laboratory Practice (GCLP) procedures and FDA guidance.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Murine-Derived; Broadly Neutralizing Antibodies; HIV Antibodies; HIV Infections; HIV-1; Humans; Mice; Neutralization Tests
PubMed: 31917969
DOI: 10.1016/j.jim.2020.112736 -
Toxins Dec 2020The use of synthetic antibody libraries and phage displays provides an efficient and robust method for the generation of antibodies against a wide range of targets with...
The use of synthetic antibody libraries and phage displays provides an efficient and robust method for the generation of antibodies against a wide range of targets with highly specific binding properties. As the in vitro selection conditions can be easily controlled, these methods enable the rapid generation of binders against difficult targets such as toxins and haptens. In this study, we used deoxynivalenol mycotoxin as a target to generate anti-idiotype-antibodies with unique binding properties from synthetic antibody libraries. The binding of the selected anti-idiotype antibodies can be efficiently inhibited with the addition of free isoforms of deoxynivalenol. The antibody was consecutively used to develop deoxynivalenol-specific ELISA and TRF-immunoassays, which can detect deoxynivalenol and two of the most common metabolic isoforms in the range of 78-115 ng/mL.
Topics: Antibodies, Anti-Idiotypic; Cell Surface Display Techniques; Immunoassay; Mycotoxins
PubMed: 33379255
DOI: 10.3390/toxins13010018 -
Preparative Biochemistry & Biotechnology 2020Immunoassay has been widely used in the screening of mycotoxins, which may be hazardous to the operator or the environment. This study was to develop a green way to...
Immunoassay has been widely used in the screening of mycotoxins, which may be hazardous to the operator or the environment. This study was to develop a green way to measure zearalenone (ZEN) with a monoclonal β-type anti-idiotype antibody (Ab2β) against ZEN in place of ZEN standard. Six monoclonal β-type anti-idiotype antibodies were prepared. The 50% inhibitory concentration (IC) value to ZEN of the six antibodies was between 34.45 ± 1.12-182.12 ± 15.40 nM. A green ELISA was then developed and validated. The quantitative conversion formula between ZEN and the monoclonal Ab2β against ZEN was = 0.092, = 0.990. The working range was 2.63-100.64 ng ml. The recovery rate in spiked feed samples was from 82.15% to 102.79%, and the within-assay and between-assay coefficient variation (CV) level were less than 10.00%. A good correlation was obtained by high-performance liquid chromatography method (HPLC) to validate the developed method.
Topics: Animal Feed; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Food Contamination; Green Chemistry Technology; Limit of Detection; Mycotoxins; Zearalenone
PubMed: 31876440
DOI: 10.1080/10826068.2019.1703195 -
Monoclonal Antibodies in... Feb 2021The PubMed data set was scanned with the title and abstract term "Idiotype" followed by secondary searches with "Vaccine" and "Clinical trial." The retrieved references...
The PubMed data set was scanned with the title and abstract term "Idiotype" followed by secondary searches with "Vaccine" and "Clinical trial." The retrieved references were analyzed from the period before and after hybridoma technology (1975). In 1963, Oudin and Kunkel discovered that antibodies against antibodies can be raised to identify determinants unique to an antibody termed idiotype or individual antigenic determinant. Two laboratories reported that anti-idiotypic antibodies can suppress specific antibody responses in mice. In 1974, Jerne proposed a network of idiotypes and anti-idiotypes and the functionality of the idiotype network was confirmed. This prompted the proposal of a symmetrical regulatory immune response. By 1989, the concept and the functional parameters of the immune idiotype network were established in the prehybridoma period. It was not until 1981 that monoclonal anti-idiotypic antibodies were used as tools to study the expression of idiotypic determinants on antibodies and to categorize functional properties in the immune network as network antigens in 1989. Hybridoma-generated monoclonal anti-idiotypic antibodies provided the tools to precisely identify different idiotypic regions on antibodies and test these as targets to induce network cascades. The initial distinction of Ab2s as alpha and beta were expanded to include gamma and delta. The initial concept of Ab2beta being an antigen internal image, used as vaccine, was challenged showing that targeting all idiotopes on B cell receptors can induce specific antibodies. After the discovery of the hybridoma technology a wave of idiotype topic publications occurred, that declined by 2015. In 1985, in this wave of reports on anti-idiotypes, their importance to vaccines dominated. These vaccines targeted in animal models parasite, bacterial, and viral diseases, and cancer. The reported data indicated a therapeutic response in inbred mice. The issue of idiotype matching between mouse haplotypes of vaccine origin and treated mice were raised. In 1995, the human clinical trials in different cancers using anti-Id vaccines were reported. Only one such vaccine received conditional approval in Argentina and Cuba, whereas the other trials failed in phase II and III. The reasons for this failure were subsequently discussed. Although the use of the Milstein and Kohler hybridoma technology and subsequently alternative methods to produce monoclonal animal and human antibodies created a new class of drugs, commonly referred as "Biological," it failed on the promise therapeutic of anti-Id vaccines.
Topics: Animals; Antibodies, Monoclonal; Epitopes; Hybridomas; Immunoglobulin Idiotypes; Mice; Technology
PubMed: 33535018
DOI: 10.1089/mab.2020.0044 -
Molekuliarnaia Biologiia 2020Methods that utilize highly specific antibodies, anti-idiotypic antibodies, various recombinant molecules with antibody properties and immunocorrection and... (Review)
Review
Methods that utilize highly specific antibodies, anti-idiotypic antibodies, various recombinant molecules with antibody properties and immunocorrection and immunoprophylaxis with the help of vaccines are in demand and are intensely developed in the field of biomedicine. Techniques to generate specific single-domain recombinant antibodies (nanobodies) and their derivatives have raised great expectations in the past years. The review considers the recent literature data on the use of nanobodies in basic research, diagnosis, and design of new immunotherapeutic agents. Special sections focus on the prospects of using nanobodies as targeted molecules of microbiota components, the use of anti-idiotypic nanobodies, and a search for promising targets for early diagnosis based on nanobodies.
Topics: Antibodies, Anti-Idiotypic; Immunotherapy; Microbiota; Single-Domain Antibodies
PubMed: 32492000
DOI: 10.31857/S0026898420030167