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      Nanobodies—Useful Tools for Allergy Treatment?

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          Abstract

          In the last decade single domain antibodies (nanobodies, V HH) qualified through their unique characteristics have emerged as accepted and even advantageous alternative to conventional antibodies and have shown great potential as diagnostic and therapeutic tools. Currently nanobodies find their main medical application area in the fields of oncology and neurodegenerative diseases. According to late-breaking information, nanobodies specific for coronavirus spikes have been generated these days to test their suitability as useful therapeutics for future outbreaks. Their superior properties such as chemical stability, high affinity to a broad spectrum of epitopes, low immunogenicity, ease of their generation, selection and production proved nanobodies also to be remarkable to investigate their efficacy for passive treatment of type I allergy, an exaggerated immune reaction to foreign antigens with increasing global prevalence.

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          Most cited references114

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          Continuous cultures of fused cells secreting antibody of predefined specificity.

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            Nanobodies: natural single-domain antibodies.

            Sera of camelids contain both conventional heterotetrameric antibodies and unique functional heavy (H)-chain antibodies (HCAbs). The H chain of these homodimeric antibodies consists of one antigen-binding domain, the VHH, and two constant domains. HCAbs fail to incorporate light (L) chains owing to the deletion of the first constant domain and a reshaped surface at the VHH side, which normally associates with L chains in conventional antibodies. The genetic elements composing HCAbs have been identified, but the in vivo generation of these antibodies from their dedicated genes into antigen-specific and affinity-matured bona fide antibodies remains largely underinvestigated. However, the facile identification of antigen-specific VHHs and their beneficial biochemical and economic properties (size, affinity, specificity, stability, production cost) supported by multiple crystal structures have encouraged antibody engineering of these single-domain antibodies for use as a research tool and in biotechnology and medicine.
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              Naturally occurring antibodies devoid of light chains.

              Random association of VL and VH repertoires contributes considerably to antibody diversity. The diversity and the affinity are then increased by hypermutation in B cells located in germinal centres. Except in the case of 'heavy chain' disease, naturally occurring heavy-chain antibodies have not been described, although antigen binding has been demonstrated for separated heavy chains or cloned VH domains. Here we investigate the presence of considerable amounts of IgG-like material of M(r) 100K in the serum of the camel (Camelus dromedarius). These molecules are composed of heavy-chain dimers and are devoid of light chains, but nevertheless have an extensive antigen-binding repertoire, a finding that calls into question the role of light chains in the camel. Camel heavy-chain IgGs lack CH1, which in one IgG class might be structurally replaced by an extended hinge. Heavy-chain IgGs are a feature of all camelids. These findings open new perspectives in the engineering of antibodies.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 September 2020
                2020
                : 11
                : 576255
                Affiliations
                [1] 1 Division of Immunopathology, Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , Vienna, Austria
                [2] 2 Institute of Gene Biology, Russian Academy of Sciences , Moscow, Russia
                Author notes

                Edited by: Christiane Hilger, Luxembourg Institute of Health, Luxembourg

                Reviewed by: Tomasz Uchanski, Luxembourg Institute of Health, Luxembourg; Simon Blank, Technical University of Munich and Helmholtz Center Munich, Germany

                *Correspondence: Sabine Flicker, sabine.flicker@ 123456meduniwien.ac.at

                This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.576255
                7561424
                33117377
                82885022-c7d2-4e97-8366-64ae88670729
                Copyright © 2020 Flicker, Zettl and Tillib

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 June 2020
                : 15 September 2020
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 114, Pages: 9, Words: 3534
                Funding
                Funded by: Austrian Science Fund 10.13039/501100002428
                Award ID: Russian Foundation for Basic Research
                Categories
                Immunology
                Mini Review

                Immunology
                allergy,allergen,nanobody,vhh,blocking antibody,allergy treatment
                Immunology
                allergy, allergen, nanobody, vhh, blocking antibody, allergy treatment

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