Publications by authors named "Thomas M Kundig"

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT.

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Synthetic mRNA produced by in vitro transcription (ivt mRNA) is the active pharmaceutical ingredient of approved anti-COVID-19 vaccines and of many drugs under development. Such synthetic mRNA typically contains several hundred bases of non-coding "untranslated" regions (UTRs) that are involved in the stabilization and translation of the mRNA. However, UTRs are often complex structures, which may complicate the entire production process.

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Chemotherapies are standard care for most cancer types. Pyrimidine analogs including 5-fluorouracil, cytosine arabinoside, 5-azacytidine, and gemcitabine are effective drugs that are utilized as part of a number of anticancer regimens. However, their lack of cell-specificity results in severe side effects.

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Interleukin-36 (IL-36) cytokines are structurally similar to other Interleukin-1 superfamily members and are essential to convey inflammatory responses at epithelial barriers including the skin, lung, and gut. Due to their potent effects on immune cells, IL-36 cytokine activation is regulated on multiple levels, from expression and activation to receptor binding. Different IL-36 isoforms convey specific responses as a consequence of particular danger- or pathogen-associated molecular patterns.

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Article Synopsis
  • Vaccines typically rely on T lymphocytes for B-cell activity and memory, but the study shows that specific peptide and adjuvant combinations can induce antibody responses without T-cell help.
  • Mice immunized with liposomes carrying 15mer peptides and monophosphoryl lipid A (MPLA) exhibited a rapid IgG class switch and long-lasting antibody responses, highlighting a novel mechanism of T-cell independent antibody production.
  • This T-cell independent response could be beneficial in situations where T-cell immunity is impaired or when immediate antibody protection is required, indicating potential for new vaccine strategies.
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During recent years, RNA therapeutics have begun to make a substantial impact in the clinic, with the approval of the siRNA-based therapeutic Patisiran in 2018, and of the two mRNA SARS-CoV-2 vaccines, BNT162b2 and mRNA-1273 in 2021. A key to the success of these therapeutics lies in the lipid-based delivery system. The therapeutic RNAs are encapsulated in lipid nanoparticles (LNPs), which protect against enzymatic degradation and efficiently deliver the RNA across the cell membrane into the cytosol.

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The recent success of the synthetic mRNA-based anti-COVID-19 vaccines has demonstrated the broad potential of the mRNA platform for applications in medicine, thanks to the combined efforts of a small community that has vastly improved key determinants such as design and formulation of synthetic mRNA during the past three decades. However, the cost of production and sensitivity to enzymatic degradation are still limiting the broader application of synthetic mRNA for therapeutic applications. The increased interest in mRNA-based technologies has spurred a renaissance for circular RNA (circRNA), as the lack of free 5' and 3' ends substantially increases resistance against enzymatic degradation in biological systems and does not require expensive cap analogs, as translation is controlled by an Internal Ribosome Entry Site (IRES) sequence.

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Objectives: Peanut allergy is an IgE-mediated food allergy that is associated with asthma in certain patients. With increasing prevalence, its great impact on the quality of life, and a lack of treatment options, the need for new therapy options is a given. Hence, models for research and development are required.

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Background: Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally.

Objective: We aim to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT.

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Background: In 2002-2005, we conducted a phase I/II clinical trial where a new allergy immunotherapy (AIT) route was introduced: intralymphatic immunotherapy (ILIT). Ultrasound guidance allowed injection of allergen directly into inguinal lymph nodes. Grass pollen-allergic patients received 3 injections with 1-month intervals.

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Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.

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Introduction: IgE-mediated bee venom allergy can be treated with allergen-specific immunotherapy (AIT). Subcutaneous immunotherapy (SCIT) is time and cost intensive due to the repeated consultations, but the costs are justified by the high risk of potentially life-threatening allergic reactions, including anaphylaxis. However, intralymphatic immunotherapy (ILIT) offers potential to reduce treatment costs due to a significant reduction in injections and a shorter duration of therapy.

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Introduction: Allergy, the immunological hypersensitivity to innocuous environmental compounds, is a global health problem. The disease triggers, allergens, are mostly proteins contained in various natural sources such as plant pollen, animal dander, dust mites, foods, fungi, and insect venoms. Allergies can manifest with a wide range of symptoms in various organs and be anything from just tedious to life-threatening.

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Background: Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus-like particles (VLPs), is described here for the treatment of peanut allergy.

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Background: Peanut allergy is a type-I hypersensitivity immune reaction mediated by the binding of peanut allergens to IgE-FcεRI complexes on mast cells and basophils and by their subsequent cellular degranulation. Of all major peanut allergens, Ara h 2 is considered the most anaphylactic. With few options but allergen avoidance, effective treatment of allergic patients is needed.

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Background: Peanut allergy accounts for the majority of food-induced hypersensitivity reactions and can lead to lethal anaphylaxis. Animal models can provide an insight into the immune mechanisms responsible for sensitization and allergic anaphylaxis. However, different mouse strains and sensitization protocols can influence the successful development of a peanut allergic mouse model.

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Nanoparticles of different sizes formulated with unmodified RNA and Protamine differentially engage Toll-like Receptors (TLRs) and activate innate immune responses . Here, we report that similar differential immunostimulation that depends on the nanoparticle sizes is induced in wild type as well as in humanized mice. In addition, we found that the schedule of injections strongly affects the magnitude of the immune response.

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Background: Subcutaneous venom immunotherapy (VIT) represents an effective treatment against bee venom allergy. However, it involves long treatment times, high costs, and the risk of adverse events (AEs). Shorter, safer, and cheaper treatment options are therefore pursued.

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Conventional vaccines are very efficient in the prevention of bacterial infections caused by extracellular pathogens due to effective stimulation of pathogen-specific antibodies. In contrast, considering that intracellular surveillance by antibodies is not possible, they are typically less effective in preventing or treating infections caused by intracellular pathogens such as . The objective of the current study was to use so-called photochemical internalization (PCI) to deliver a live bacterial vaccine to the cytosol of antigen-presenting cells (APCs) for the purpose of stimulating major histocompatibility complex (MHC) I-restricted CD8 T-cell responses.

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Introduction: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), substantial effort has been made to gain knowledge about the immunity elicited by infection or vaccination.

Methods: We studied the kinetics of antibodies and virus neutralisation induced by vaccination with BNT162b2 in a Swiss cohort of SARS-CoV-2 naïve (n = 40) and convalescent (n = 9) persons. Blood sera were analysed in a live virus neutralisation assay and specific IgG and IgA levels were measured by enzyme-linked immunoassay and analysed by descriptive statistics.

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Article Synopsis
  • Psoriasis is a chronic skin condition linked to imbalanced cytokine signaling, with new drugs targeting the IL-23p19 subunit showing greater effectiveness than those that also block IL-12.
  • Researchers developed a special mouse model to study the role of IL-12 in psoriasis, finding it expressed in T cells and certain skin cells, and discovered that its absence in keratinocytes worsened the disease.
  • The study suggests that IL-12 helps control skin cell growth and maintain the skin barrier, providing a possible explanation for the better results seen with IL-23p19 inhibitors compared to older treatments.
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The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries.

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