The rationale for development of ligelizumab in food allergy.

Food allergy (FA) is a growing healthcare problem worldwide and the rising prevalence in many countries can be attributed to lifestyle, environmental, and nutritional changes. Immunoglobulin E (IgE)-mediated FA is the most common form of FA affecting approximately 3%-10% of adults and 8% of children across the globe. Food allergen-induced immediate hypersensitivity reactions mediated by IgE and high-affinity IgE receptor (FcεRI) complexes on mast cells and basophils are a major hallmark of the disease. FA can affect several aspects of health-related quality of life and impose a substantial financial burden on patients and healthcare systems. Although currently there is one United States Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved treatment for peanut allergy (Palforzia), the main treatment approaches are based on allergen avoidance and symptom management. Thus, there is an urgent need for more effective and ideally disease-modifying strategies. Given the crucial role of IgE in FA, anti-IgE monoclonal antibodies are considered promising therapeutic agents. Talizumab was the first humanized anti-IgE antibody to demonstrate substantial protection against allergic reactions from accidental peanut exposure by substantially increasing the peanut reactivity threshold on oral food challenge. However, development of talizumab was discontinued and further trials were performed using omalizumab. In double-blind, Phase 2, placebo-controlled trials in patients with multi-FAs, sustained dosing with omalizumab, or omalizumab in combination with oral immunotherapy, enabled rapid desensitization to multiple trigger foods. In this review, we describe the development of ligelizumab (a derivative of talizumab), a next generation, humanized monoclonal anti-IgE antibody, its existing clinical evidence, and its potential in the management of FA. When compared with omalizumab, ligelizumab binds with ∼88-fold higher affinity for human IgE and recognizes a different epitope that substantially overlaps with the binding site of FcεRI. These properties translate into a high potency to block IgE/FcεRI signaling in both in vitro and in vivo studies. Given its efficient suppression of IgE levels, good safety and pharmacokinetic/pharmacodynamic profile, ligelizumab clearly warrants further studies for the potential management of FA

Glycan-specific IgG anti-IgE autoantibodies are protective against allergic anaphylaxis in a murine model.

BACKGROUND IgE causes anaphylaxis in type-1 hypersensitivity diseases by activating degranulation of effector cells such as mast cells and basophils. The mechanisms that control IgE activity and prevent anaphylaxis under normal conditions are still enigmatic. OBJECTIVE We aimed to unravel how anti-IgE autoantibodies are induced and understand their role in regulating serum IgE level and allergic anaphylaxis. METHODS We immunized mice with different forms of IgE and tested anti-IgE autoantibody responses and their specificities. We then analysed the effect of those antibodies on serum kinetics and their in vitro and in vivo impact on anaphylaxis. Finally, we investigated anti-IgE autoantibodies in human sera. RESULTS Immunization of mice with IgE-immune complexes induced glycan-specific anti-IgE autoantibodies. The anti-IgE autoantibodies prevented effector cell sensitization, reduced total IgE serum levels, protected mice from passive and active IgE sensitization, and resulted in cross-protection against different allergens. Furthermore, glycan-specific anti-IgE autoantibodies were present in sera from allergic and non-allergic subjects. CONCLUSION In conclusion, we provide first evidence that in the murine model the serum level and anaphylactic activity of IgE may be down-regulated by glycan-specific IgG anti-IgE autoantibodies

Exposure to avian coronavirus vaccines is associated with increased levels of SARS-CoV-2-cross-reactive antibodies.

BACKGROUND Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. METHODS We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. RESULTS A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared with pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared with pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. CONCLUSION We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID-19

Exposure to avian coronavirus vaccines is associated with increased levels of SARS-CoV-2-cross-reactive antibodies

Background: Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. Methods: We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. Results: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared with pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared with pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. Conclusion: We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID-19. Keywords: COVID-19; IBV; SARS-CoV-2; cross-reactivity; neutralizatio

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Khresmoi Professional: Multilingual Semantic Search for Medical Professionals

There is increasing interest in and need for innovative solutions to medical search. In this paper we present the EU funded Khresmoi medical search and access system, currently in year 3 of 4 of development across 12 partners . The Khresmoi system uses a component based architecture housed in the cloud to allow for the development of several innovative applications to support target users medical information needs. The Khresmoi search systems based on this architecture have been designed to support the multilingual and multimod al information needs of three target groups the general public, general practitioners and consultant radiologists. In this paper we focus on the presentation of the systems to support the latter two groups using semantic, multilingual text and image based (including 2D and 3D radiology images) search

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Calibration of the CMS Drift Tube Chambers and Measurement of the Drift Velocity with Cosmic Rays

Peer reviewe

CMS Data Processing Workflows during an Extended Cosmic Ray Run

Peer reviewe

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe