Epitope mapping of antibodies induced with a conserved rhinovirus protein generating protective anti-rhinovirus immunity

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations. Currently there is no vaccine for RV which is largely due to the existence of ~160 serotypes/strains. We demonstrated previously that immunising mice with highly conserved VP4 and VP2 regions of the RV polyprotein (RV-A16 VP0) generated cross-reactive immunity to RV in vivo. The current study investigated and mapped the epitopes of RV-A16 VP0 that are targets for antibodies in serum samples from VP0 immunisation and RV challenge studies in mice. Recombinant capsid proteins, peptide pools and individual peptides spanning the immunogen sequence (RV-A16 VP0) were assessed for IgG binding sites to identify epitopes. We found that peptide pools covering the C-terminus of VP4, the N-terminus of VP2 and the neutralising NIm-II site within VP2 were bound by serum IgG from immunised mice. The NIm-II site peptide pool blocked IgG binding to the immunogen RV-A16 VP0 and individual peptides within the pool binding IgG were further mapped. Thus, we have identified immunodominant epitopes of RV vaccine candidate RV-A16 VP0, noting that strong IgG binding antibodies were observed that target a key neutralising epitope that is highly variable amongst RV serotypes

Supplementary data for the article: Apostolovic, D.; Sánchez-Vidaurre, S.; Waden, K.; Curin, M.; Grundström, J.; Gafvelin, G.; Cirkovic Velickovic, T.; Grönlund, H.; Thomas, W. R.; Valenta, R.; et al. The Cat Lipocalin Fel d 7 and Its Cross-Reactivity with the Dog Lipocalin Can f 1. Allergy: European Journal of Allergy and Clinical Immunology 2016, 71 (10), 1490–1495. https://doi.org/10.1111/all.12955

Supplementary material for: [https://doi.org/10.1111/all.12955]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2337]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3650

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

High-accuracy determination of the U 238 / U 235 fission cross section ratio up to ≈1 GeV at n-TOF at CERN

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOIThe U238 to U235 fission cross section ratio has been determined at n-TOF up to ≈1 GeV, with two different detection systems, in different geometrical configurations. A total of four datasets has been collected and compared. They are all consistent to each other within the relative systematic uncertainty of 3-4%. The data collected at n-TOF have been suitably combined to yield a unique fission cross section ratio as a function of neutron energy. The result confirms current evaluations up to 200 MeV. Good agreement is also observed with theoretical calculations based on the INCL++/Gemini++ combination up to the highest measured energy. The n-TOF results may help solve a long-standing discrepancy between the two most important experimental datasets available so far above 20 MeV, while extending the neutron energy range for the first time up to ≈1 GeV.Peer reviewedFinal Published versio

Towards the high-accuracy determination of the 238U fission cross section at the threshold region at CERN - N-TOF

The 238U fission cross section is an international standard beyond 2 MeV where the fission plateau starts. However, due to its importance in fission reactors, this cross-section should be very accurately known also in the threshold region below 2 MeV. The 238U fission cross section has been measured relative to the 235U fission cross section at CERN - n-TOF with different detection systems. These datasets have been collected and suitably combined to increase the counting statistics in the threshold region from about 300 keV up to 3 MeV. The results are compared with other experimental data, evaluated libraries, and the IAEA standards

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen

Rhinitis associated with asthma is distinct from rhinitis alone: TARIA‐MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis.info:eu-repo/semantics/publishedVersio

Birth cohorts in asthma and allergic diseases: Report of a NIAID/NHLBI/MeDALL joint workshop

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. Over 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A NIAID (National Institute of Allergy and Infectious Diseases), NHLBI (National Heart Lung and Blood Institute), MeDALL (Mechanisms of the Development of Allergy, Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, MD, USA September 11–12, 2012 with 3 objectives (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development and (5) harmonization of existing birth cohorts. This manuscript presents the workgroup reports and provides web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu) where the reader will find tables describing the characteristics of the birth cohorts included in this report, type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts