VHH Antibody Applications

VHH Antibody Applications


Discovered in the early 1990s, VHH antibodies, derived from heavy-chain-only IgG antibodies in the Camelidae family, present unique and exceptional potential in diverse fields of research and medicine. Their distinct properties, including small size, excellent solubility, superior stability, low immunogenicity, efficient tissue penetration, and industrialised production, set them apart from conventional mAbs. In research, VHH antibodies serve as exquisite tools for studies in structural, cell, and developmental biology. Additionally, their demonstrated efficacy in enhancing the sensitivity of diagnostic tests underscores their versatility. Beyond diagnostics, several constructs based on VHH antibodies have been strategically designed to pave the way for the development of innovative therapeutic products.

VHH Antibody Structure

VHH shares common domains with conventional antibody VH, encompassing the conserved framework regions (FR1, FR2, FR3, and FR4) and the complementarity-determining regions (CDR1, CDR2, and CDR3). Notably, VH in conventional antibodies exhibits four highly conserved hydrophobic amino acids (V37, G44, L45, and W47) within FR2. In contrast, VHH antibodies replace these residues with hydrophilic counterparts (F37, E45, R47, and G52), augmenting the solubility of VHH antibodies. In addition, the average length of CDR1 and CDR3 of VHH is a bit longer than VH. The flexible CDR3 loop of VHHs could form finger-like extensions and reach cavities that target antigens inaccessible to conventional mAbs. The linkage of CDR1 with CDR3 is usually achieved by an interloop disulfide bond, to improve the conformational stability of VHHs.

Conventional mAb, HCAb, and VHH

VH and VHH in structure

Asaadi et al., (2021).
Su et al., (2022).
Jin et al., (2023).

Workflow of Abnova NanoAb™ – VHH Antibodies

Applications of VHH Antibody

Basic Research

  • Efficient Antigen Capture: VHH antibodies, with their small size, efficiently capture antigens, enabling focused studies on specific molecular targets.
  • Structural Biology: VHH antibodies assist in crystallising proteins, resolving co-crystals, and gaining in-depth insights into molecular structures.
  • Intracellular Imaging: Highly stable VHH antibodies can be expressed inside cells, tracking antigens within live cells.
  • Super-resolution Microscopy: Fluorescently labelled VHH antibodies are utilised in super-resolution microscopy, enhancing the visualisation of cellular structures.
  • Functional Tools in Enzymology: VHH antibodies serve as functional tools, regulating enzyme activity and providing insights into enzyme intermediates and mechanisms.
  • Nuclear Magnetic Resonance (NMR) Studies: VHH antibodies are valuable in NMR studies, monitoring protein dynamics.

Clinical Potential

  • Enhanced Diagnostic Precision: VHH antibodies elevate sensitivity and specificity in clinical diagnostics, enhancing the precision of biomarker detection.
  • Molecular Imaging Advancements: Functioning as molecular imaging agents, VHH antibodies proficiently visualise disease-related biomolecules, contributing to advancements in diagnostic imaging.
  • Biosensors for Real-Time Detection: VHH antibodies integrated into biosensors detect disease-specific markers in real time, providing accurate and timely information.
  • Targeted Therapeutic Potential: VHH antibodies hold therapeutic promise in diverse clinical conditions, allowing design for targeted drug delivery to disease cells, and minimising harm to healthy tissues.
  • Immunomodulation Possibilities: Engineered VHH antibodies may play a role in immunomodulatory therapies, serving as potential candidates for autoimmune conditions.
  • Neurological Disorder Treatment: VHH antibodies exhibit potential in treating neurological disorders by targeting specific proteins involved in neurodegenerative diseases, offering a focused therapeutic approach.

Global Approved VHH Antibodies

Jin et al., (2023).
Markham et al., (2022).

Originally posted by Abnova on: https://www.abnova.com/en-global/newsletter/newsletter/content/newsletter2024-01-01

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VHH Antibody Applications
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