Molecular engineering of nanobodies as tools in allergology: diagnostics and beyond

Aagaard, Josephine Baunvig; Ballegaard, Anne‐Sofie Ravn; Andersen, Paul; Spillner, Edzard

doi:10.1007/s40629-023-00261-w

Cited by 4 publications

(2 citation statements)

References 76 publications

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“…While allergen-specific nanobodies as tools for food surveillance to identify traces of nut, lupine, and milk allergen contaminants have already been explored, the application of allergen-specific nanobodies as biologics for allergy prevention or treatment is a rather new endeavour ( 31 – 33 , 36 , 55 – 57 ). Passive administration of allergen-specific monoclonal antibodies has lately been proven to provide a fast and efficient treatment option for allergies ( 21 , 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…To overcome this challenge, gene-based approaches and various delivery modes of monoclonal antibodies such as inhalation or intranasal application have emerged as promising and advantageous options ( 27 , 29 ). In parallel, nanobodies have recently been discovered as potentially appropriate tools for allergy treatment ( 30 – 36 ). Their unique features such as their capacity to bind epitopes on their cognate antigens with a strong affinity that may not be accessible for monoclonal antibodies, their single domain organization, their easy and inexpensive generation in prokaryotic cells, render nanobodies valuable agents for food safety inspections but also for nanobody-mediated interventional studies ( 31 , 32 , 36 – 38 ).…”

Section: Introductionmentioning

confidence: 99%

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Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Bauernfeind,

Zettl,

Ivanova

et al. 2024

Front. Immunol.

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BackgroundAround 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions. A recent study provided evidence for the first time that Bet v 1-specific nanobodies reduce patients´ IgE binding to Bet v 1. In order to increase the potential to outcompete IgE recognition of Bet v 1 and to foster cross-reactivity and cross-protection, we developed Bet v 1-specific nanobody trimers and evaluated their capacity to suppress polyclonal IgE binding to corresponding allergens and allergen-induced basophil degranulation.MethodsNanobody trimers were engineered by adding isoleucine zippers, thus enabling trimeric formation. Trimers were analyzed for their cross-reactivity, binding kinetics to Bet v 1, and related allergens, and patients’ IgE inhibition potential. Finally, their efficacy to prevent basophil degranulation was investigated.ResultsTrimers showed enhanced recognition of cross-reactive allergens and increased efficiency to reduce IgE-allergen binding compared to nanobody monomers. Furthermore, trimers displayed slow dissociation rates from allergens and suppressed allergen-induced mediator release.ConclusionWe generated high-affine nanobody trimers that target Bet v 1 and related allergens. Trimers blocked IgE-allergen interaction by competing with IgE for allergen binding. They inhibited IgE-mediated release of biological mediators, demonstrating a promising potential to prevent allergic reactions caused by Bet v 1 and relatives.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Bauernfeind,

Zettl,

Ivanova

et al. 2024

Front. Immunol.

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Aspergillus-assoziierte Erkrankungen aus infektiologischer und allergologischer Perspektive

Stemler,

Nacov,

Sprute

et al. 2024

Allergo J

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Aspergillus-associated diseases from an infectious diseases and allergological perspective

Stemler,

Nacov,

Sprute

et al. 2024

Allergo J Int

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Aspergillus-associated diseases are rare and pose challenges for practitioners. Diagnosis is complex and requires rational, targeted, and multidisciplinary collaboration, as well as a high degree of expertise and an individualized approach. For the infectious diseases physician, the focus is on the question of infection or colonization. In severely immunocompromised patients, invasive aspergillosis occurs, which most frequently affects the lungs (IPA) and is characterized by invasive, destructive growth. This acute clinical picture is associated with a high mortality rate. Chronic pulmonary aspergillosis (CPA) develops on the basis of pre-existing changes in lung structure caused by other pulmonary diseases and often requires surgical treatment. Another chronic form is allergic bronchopulmonary aspergillosis (ABPA). It is often associated with bronchiectasis in patients with bronchial asthma or cystic fibrosis. Sinus mycoses are divided into non-invasive and invasive forms, which can occur in immunocompromised patients and most commonly affect the maxillary sinus. Here, local surgical measures are an obligatory part of treatment, whereas the non-invasive form usually has an allergic component. In addition, drug-based antifungal and/or anti-inflammatory therapy is used for all entities.

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Molecular engineering of nanobodies as tools in allergology: diagnostics and beyond

Cited by 4 publications

References 76 publications

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Aspergillus-assoziierte Erkrankungen aus infektiologischer und allergologischer Perspektive

Aspergillus-associated diseases from an infectious diseases and allergological perspective

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