Nanobodies in the fight against infectious diseases: repurposing nature&apos;s tiny weapons

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Abstract

Nanobodies are the smallest known antigen-binding molecules to date. Their small size, good tissue penetration, high stability and solubility, ease of expression, refolding ability, and negligible immunogenicity in the human body have granted them excellence over conventional antibodies. Those exceptional attributes of nanobodies make them promising candidates for various applications in biotechnology, medicine, protein engineering, structural biology, food, and agriculture. This review presents an overview of their structure, development methods, advantages, possible challenges, and applications with special emphasis on infectious diseases-related ones. A showcase of how nanobodies can be harnessed for applications including neutralization of viruses and combating antibiotic-resistant bacteria is detailed. Overall, the impact of nanobodies in vaccine design, rapid diagnostics, and targeted therapies, besides exploring their role in deciphering microbial structures and virulence mechanisms are highlighted. Indeed, nanobodies are reshaping the future of infectious disease prevention and treatment.

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Most cited references 183

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Nanobodies: natural single-domain antibodies.

Serge Muyldermans (2013)

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.

C. Hamers-Casterman, T Atarhouch, S Muyldermans … (1993)

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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The Therapeutic Potential of Nanobodies

Ivana Jovčevska, Serge Muyldermans (2019)

Today, bio-medical efforts are entering the subcellular level, which is witnessed with the fast-developing fields of nanomedicine, nanodiagnostics and nanotherapy in conjunction with the implementation of nanoparticles for disease prevention, diagnosis, therapy and follow-up. Nanoparticles or nanocontainers offer advantages including high sensitivity, lower toxicity and improved safety—characteristics that are especially valued in the oncology field. Cancer cells develop and proliferate in complex microenvironments leading to heterogeneous diseases, often with a fatal outcome for the patient. Although antibody-based therapy is widely used in the clinical care of patients with solid tumours, its efficiency definitely needs improvement. Limitations of antibodies result mainly from their big size and poor penetration in solid tissues. Nanobodies are a novel and unique class of antigen-binding fragments, derived from naturally occurring heavy-chain-only antibodies present in the serum of camelids. Their superior properties such as small size, high stability, strong antigen-binding affinity, water solubility and natural origin make them suitable for development into next-generation biodrugs. Less than 30 years after the discovery of functional heavy-chain-only antibodies, the nanobody derivatives are already extensively used by the biotechnology research community. Moreover, a number of nanobodies are under clinical investigation for a wide spectrum of human diseases including inflammation, breast cancer, brain tumours, lung diseases and infectious diseases. Recently, caplacizumab, a bivalent nanobody, received approval from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treatment of patients with thrombotic thrombocytopenic purpura.

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Author and article information

Contributors

Ahmed S. Attia: ahmed.attia@pharma.cu.edu.eg

Journal

Journal ID (nlm-ta): World J Microbiol Biotechnol

Journal ID (iso-abbrev): World J Microbiol Biotechnol

Title: World Journal of Microbiology & Biotechnology

Publisher: Springer Netherlands (Dordrecht )

ISSN (Print): 0959-3993

ISSN (Electronic): 1573-0972

Publication date (Electronic): 21 May 2024

Publication date PMC-release: 21 May 2024

Publication date (Print): 2024

Volume: 40

Issue: 7

Electronic Location Identifier: 209

Affiliations

[1 ]Microbiology and Immunology Postgraduate Program, Faculty of Pharmacy, Cairo University, ( https://ror.org/03q21mh05) Cairo, 11562 Egypt

[2 ]Department of Medical Sciences, Faculty of Dentistry, The British University in Egypt, El Sherouk City, ( https://ror.org/0066fxv63) Cairo, 11837 Egypt

[3 ]Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, ( https://ror.org/03q21mh05) Cairo, 11562 Egypt

Article

Publisher ID: 3990

DOI: 10.1007/s11274-024-03990-4

PMC ID: 11108896

PubMed ID: 38771414

SO-VID: 951a6dd5-e6f4-4478-a5f7-efee869cad31

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 20 February 2024

Date accepted : 15 April 2024

Funding

Funded by: Academy of Scientific Research and Technology (ASRT), Egypt

Award ID: D62/2020

Award Recipient : Soha S. Rizk Dina M. Moustafa Shahira A. ElBanna Hanzada T. Nour El-Din Ahmed S. Attia

Funded by: Cairo University

Open Access :

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

Custom metadata

ScienceOpen disciplines: Biotechnology

Keywords: bacteria,diagnosis,infectious diseases,nanobodies,prophylaxis,treatment,viruses

Data availability:

ScienceOpen disciplines: Biotechnology

Keywords: bacteria, diagnosis, infectious diseases, nanobodies, prophylaxis, treatment, viruses

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