Application of camelid heavy-chain variable domains (VHHs) in prevention and treatment of bacterial and viral infections.

Wilken, Lucas; McPherson, Anne

Abstract

Camelid heavy-chain variable domains (VHHs) are the smallest, intact, antigen-binding units to occur in nature. VHHs possess high degrees of solubility and robustness enabling generation of multivalent constructs with increased avidity - characteristics that mark their superiority to other antibody fragments and monoclonal antibodies. Capable of effectively binding to molecular targets inaccessible to classical immunotherapeutic agents and easily produced in microbial culture, VHHs are considered promising tools for pharmaceutical biotechnology. With the aim to demonstrate the perspective and potential of VHHs for the development of prophylactic and therapeutic drugs to target diseases caused by bacterial and viral infections, this review article will initially describe the structural features that underlie the unique properties of VHHs and explain the methods currently used for the selection and recombinant production of pathogen-specific VHHs, and then thoroughly summarize the experimental findings of five distinct studies that employed VHHs as inhibitors of host-pathogen interactions or neutralizers of infectious agents. Past and recent studies suggest the potential of camelid heavy-chain variable domains as a novel modality of immunotherapeutic drugs and a promising alternative to monoclonal antibodies. VHHs demonstrate the ability to interfere with bacterial pathogenesis by preventing adhesion to host tissue and sequestering disease-causing bacterial toxins. To protect from viral infections, VHHs may be employed as inhibitors of viral entry by binding to viral coat proteins or blocking interactions with cell-surface receptors. The implementation of VHHs as immunotherapeutic agents for infectious diseases is of considerable potential and set to contribute to public health in the near future.

Citation

WILKEN, L. and MCPHERSON, A. 2018. Application of camelid heavy-chain variable domains (VHHs) in prevention and treatment of bacterial and viral infections. International reviews of immunology [online], 37(1), pages 69-76. Available from: https://doi.org/10.1080/08830185.2017.1397657

• Journal Article Type: Article
• Acceptance Date: Aug 22, 2017
• Online Publication Date: Nov 28, 2017
• Publication Date: Feb 28, 2018
• Deposit Date: Mar 16, 2018
• Publicly Available Date: Nov 29, 2018
• Journal: International reviews of immunology
• Print ISSN: 0883-0185
• Electronic ISSN: 1563-5244
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 37
• Issue: 1
• Pages: 69-76
• DOI: https://doi.org/10.1080/08830185.2017.1397657
• Keywords: Immunotherapy; Infectious disease; Nanobodies; Single domain antibody
• Public URL: http://hdl.handle.net/10059/2804