Plug and play virus-like particles for the generation of anti-toxin antibodies

Edge, Rebecca, Marriott, Amy, Stars, Emma, Patel, Rohit, Wilkinson, Mark ORCID: https://orcid.org/0000-0003-3109-6888, King, Lloyd D.W., Slagboom, Julien, Tan, Choo Hock, Ratanabanangkoon, Kavi, Draper, Simon J. and Ainsworth, Stuart ORCID: https://orcid.org/0000-0002-0199-6482 (2024) 'Plug and play virus-like particles for the generation of anti-toxin antibodies'. Toxicon: X, Vol 23, e100204.

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Abstract

Snakebite is a major global health concern, for which antivenom remains the only approved treatment to neutralise the harmful effects of the toxins. However, some medically important toxins are poorly immunogenic, resulting in reduced efficacy of the final product. Boosting the immunogenicity of these toxins in the commercial antivenom immunising mixtures could be an effective strategy to improve the final dose efficacy, and displaying snake antigens on Virus-like particles (VLPs) is one method for this. However, despite some applications in the field of snakebite, VLPs have yet to be explored in methods that could be practical at an antivenom manufacturing scale. Here we describe the utilisation of a “plug and play” VLP system to display immunogenic linear peptide epitopes from three finger toxins (3FTxs) and generate anti-toxin antibodies. Rabbits were immunised with VLPs displaying individual consensus linear epitopes and their antibody responses were characterised by immunoassay. Of the three experimental consensus sequences, two produced antibodies capable of recognising the consensus peptides, whilst only one of these could also recognise native whole toxins. Further characterisation of antibodies raised against this peptide demonstrated a sub-class specific response, and that these were able to elicit partially neutralising antibody responses, resulting in increased survival times in a murine snakebite envenoming model.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 630 Toxins. Antitoxins
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.toxcx.2024.100204
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	16 Sep 2024 13:58
Last Modified:	02 Dec 2024 08:38
URI:	https://archive.lstmed.ac.uk/id/eprint/25233

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