A human monoclonal antibody based immunoenzymetric assay to measure Fel d 1 concentrations in cat hair and pelt allergenic extracts.

In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel.

The Potential of Human Monoclonal IgE Antibodies to Establish Biological Potency and Stability of Allergen Extracts.

Purpose Of Review: Allergenic extracts are often standardized to control for potency, either by measuring concentrations of major allergens or "overall allergenicity" by competition for IgE in pooled sera from highly allergic subjects with a reference extract. Recent developments present an opportunity to use human mAb cloned from highly allergic subjects to define potency of allergenic extracts.

Recent Findings: Two recent developments present an opportunity for revising potency measurements of allergen extracts: cloning allergen specific IgE from allergic subjects and extensive epitope mapping of major allergenic proteins.

An enhanced three-stage design with trend analysis for allergen immunotherapy trials.

We previously introduced a three-stage design and associated end-of-stage analyses for allergen immunotherapy (AIT) trials. End-of-stage differences alone may not provide a fuller picture of Stages 2 and 3 effects because they may depend upon stage-specific durations. Therefore, we introduce an additional trend analysis to evaluate the difference in progression curves of two groups over the entire stage.

Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

Background: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e.

A regulator's view on AIT clinical trials in the United States and Europe: Why successful studies fail to support licensure.

Clinical studies demonstrate that efficacy and safety in allergen immunotherapy (AIT) are linked to a multiplicity of factors decisively influencing success or failure. In recent years, numerous trials were performed with correspondent study results published. Yet, the number of AIT products successfully obtaining licensure in the analogous time frame is comparably limited.

A three-stage design for allergen immunotherapy trials.

Background: Clinical trials of allergen immunotherapy (AIT) may require up to 5 years to complete. These lengthy trials may be complicated by high and potentially differential dropouts, especially among participants who perceive that they are receiving placebo. We propose a three-stage design in which the placebo group in Stage 1 crosses over to receive active treatment in Stage 2.

The History, Present and Future of Allergen Standardization in the United States and Europe.

The topic of standardization in relation to allergen products has been discussed by allergists, regulators, and manufacturers for a long time. In contrast to synthetic medicinal products, the natural origin of allergen products makes the necessary comparability difficult to achieve. This holds true for both aspects of standardization: Batch-to-batch consistency (or product-specific standardization) and comparability among products from different manufacturers (or cross-product comparability).

Technical standards in allergen exposure chambers worldwide - an EAACI Task Force Report.

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials.

Diversity and complexity of mouse allergens in urine, house dust, and allergen extracts assessed with an immuno-allergomic approach.

Background: Mouse allergy is an important cause of indoor asthma and allergic rhinoconjunctivitis. The major mouse allergen, Mus m 1, is a complex of homologous pheromone-binding lipocalins called major urinary proteins (MUPs).

Methods: We analyzed the proteome of MUPs in mouse urine, commercial mouse epithelial extracts, and environmental samples using several approaches.

Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible.

Shared and Unique Features of Human Interferon-Beta and Interferon-Alpha Subtypes.

Type I interferons (IFN-I) were first discovered as an antiviral factor by Isaacs and Lindenmann in 1957, but they are now known to also modulate innate and adaptive immunity and suppress proliferation of cancer cells. While much has been revealed about IFN-I, it remains a mystery as to why there are 16 different IFN-I gene products, including IFNβ, IFNω, and 12 subtypes of IFNα. Here, we discuss shared and unique aspects of these IFN-I in the context of their evolution, expression patterns, and signaling through their shared heterodimeric receptor.

EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines.

The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose.

Oral Immunotherapy for Food Allergy-a US Regulatory Perspective.

The recent approval of Palforzia for treatment of peanut allergy by the US Food and Drug Administration (USFDA) predicts that additional products for oral immunotherapy (OIT) are on the horizon. In this article, the authors review the legal framework by which the USFDA regulates products for OIT of food allergy and the clinical data that demonstrated that the safety and effectiveness profile of Palforzia supported approval and conclude with a discussion of oral food challenge (OFC) as a clinical endpoint to demonstrate safety and effectiveness of OIT products.

Measurement of German cockroach allergens and their isoforms in allergen extracts with mass spectrometry.

Background: Allergen extracts are the primary tool for diagnosis and treatment of allergic diseases. In the United States, most allergen extracts are non-standardized. More sophisticated analytical approaches are needed to characterize these products and enable manufacturers and regulators to better determine potency.

Perspectives in allergen immunotherapy: 2019 and beyond.

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future.

Gender differences in innate responses and gene expression profiles in memory CD4 T cells are apparent very early during acute simian immunodeficiency virus infection.

Gender differences in Human immunodeficiency virus (HIV) disease progression and comorbidities have been extensively reported. Using the simian immunodeficiency virus (SIV) infected rhesus macaque model, we show that these differences are apparent very early during the course of infection. Though there were no major changes in the proportions of CD4 T cells or its subsets, central memory CD4 T cells from female macaques were found to differentially regulate a significantly larger number of genes at day 4 post-infection (PI) as compared to males.

Lack of Activation Marker Induction and Chemokine Receptor Switch in Human Neonatal Myeloid Dendritic Cells in Response to Human Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) infects and causes disease in infants and reinfects with reduced disease throughout life without significant antigenic change. In contrast, reinfection by influenza A virus (IAV) largely requires antigenic change. The adaptive immune response depends on antigen presentation by dendritic cells (DC), which may be too immature in young infants to induce a fully protective immune response against RSV reinfections.

IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response.

Viral defense at mucosal sites depends on interferons (IFN) and IFN stimulated genes (ISGs), either of which may be constitutively expressed to maintain an "antiviral state" (AVS). However, the mechanisms that govern the AVS are poorly defined. Using a BEAS-2B respiratory epithelial cell line deficient in IRF1, we demonstrate higher susceptibility to infection with vesicular stomatitis virus (VSV) and influenza virus.

S27 of IFNα1 Contributes to Its Low Affinity for IFNAR2 and Weak Antiviral Activity.

Type I interferons (IFNs) signal by forming a high affinity IFN-IFNAR2 dimer, which subsequently recruits IFNAR1 to form a ternary complex that initiates JAK/STAT signaling. Among the 12 IFNα subtypes, IFNα1 has a uniquely low affinity for IFNAR2 (<100 × of the other IFNα subtypes) and commensurately weak antiviral activity, suggesting an undefined function distinct from suppression of viral infections. Also unique in IFNα1 is substitution of a serine for phenylalanine at position 27, a contact point that stabilizes the IFNα:IFNAR2 hydrophobic interface.

Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development.

Background: Virus-associated febrile lower respiratory tract infections (fLRIs) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defense capacity during this period, as exemplified by production of type 1 and 3 interferons (T1/3IFNs), might be an underlying determinant of risk.

Objective: We sought to investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze.

Strand-Specific Dual RNA Sequencing of Bronchial Epithelial Cells Infected with Influenza A/H3N2 Viruses Reveals Splicing of Gene Segment 6 and Novel Host-Virus Interactions.

Host-influenza virus interplay at the transcript level has been extensively characterized in epithelial cells. Yet, there are no studies that simultaneously characterize human host and influenza A virus (IAV) genomes. We infected human bronchial epithelial BEAS-2B cells with two seasonal IAV/H3N2 strains, Brisbane/10/07 and Perth/16/09 (reference strains for past vaccine seasons) and the well-characterized laboratory strain Udorn/307/72.

Differential Responses by Human Respiratory Epithelial Cell Lines to Respiratory Syncytial Virus Reflect Distinct Patterns of Infection Control.

Respiratory syncytial virus (RSV) infects small foci of respiratory epithelial cells via infected droplets. Infection induces expression of type I and III interferons (IFNs) and proinflammatory cytokines, the balance of which may restrict viral replication and affect disease severity. We explored this balance by infecting two respiratory epithelial cell lines with low doses of recombinant RSV expressing green fluorescent protein (rgRSV).