Toxin-centric development approach for next-generation antivenoms

Abstract

 Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Antibody Cross-Reactivity in Antivenom Research

“…In turn, this may help guide expansion of use for existing antivenoms and the development of future antivenoms, as well as possibly becoming a key driver for building testable hypotheses on how toxins and antibodies interact and how neutralization occurs for different toxin families [ 6 , 24 ]. Such knowledge is relevant for conventional antivenom development and manufacturing, but may become even more essential for the development of next generation antivenoms, which follow a more toxin-centric instead of a species-centric development approach [ 101 ]. Expanding our knowledge and toolbox in the field of antivenom cross-reactivity will hopefully support antibody research in the field of toxinology and in other fields.…”

Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

“…A toxin-centric approach might be the basis of next-generation snakebite treatment [ 33 ]. As described by Laustsen, snake venom is likely to be the “most complex pharmaceutical target” known, composed of a multitude of toxin components and complex biochemical interactions [ 34 ].…”

Integrating Engineering, Manufacturing, and Regulatory Considerations in the Development of Novel Antivenoms

“…The fundamental reason for this is that antivenoms comprise antibodies that are raised in direct response to the venoms included in the immunization mixture employed in their manufacture. This has the implication that venom compositions have a determining role for the immunological response raised in the production animal, and therefore affect the final antibody composition of the antivenom [ 28 ]. This situation is different for future novel antivenoms based on specifically selected mAbs.…”

“…This situation is different for future novel antivenoms based on specifically selected mAbs. Here, antibodies are discovered and carefully selected against specific isolated toxins using biotechnological methods [ 29 ] and guided by omics technologies [ 21 ] (particularly toxicovenomics [ 30 , 31 , 32 ]), which may possibly also offer the possibility of developing antibodies that have broad specificity against entire toxin subfamilies [ 28 ]. This may allow for novel rational design strategies that provide the possibility of developing mAb-based antivenoms with the ability to neutralize venoms from a broader range of species across a larger geographic area, as the antibody compositions of such antivenoms can be tailored to specifications.…”