Abstract
Antivenom cross-reactivity has been investigated for decades to determine which antivenoms can be used to treat snakebite envenomings from different snake species. Traditionally, the methods used for analyzing cross-reactivity have been immunodiffusion, immunoblotting, enzyme-linked immunosorbent assay (ELISA), enzymatic assays, and in vivo neutralization studies. In recent years, new methods for determination of cross-reactivity have emerged, including surface plasmon resonance, antivenomics, and high-density peptide microarray technology. Antivenomics involves a top-down assessment of the toxin-binding capacities of antivenoms, whereas high-density peptide microarray technology may be harnessed to provide in-depth knowledge on which toxin epitopes are recognized by antivenoms. This review provides an overview of both the classical and new methods used to investigate antivenom cross-reactivity, the advantages and disadvantages of each method, and examples of studies using the methods. A special focus is given to antivenomics and high-density peptide microarray technology as these high-throughput methods have recently been introduced in this field and may enable more detailed assessments of antivenom cross-reactivity.
Highlights
Snakebite envenoming was added to the list of the world’s most neglected tropical diseases by theWorld Health Organization in 2017 [1]
We provide an overview of the approaches used to investigate antivenom cross-reactivity towards different toxins and whole venoms
A special focus is granted to antivenomics and high-density peptide microarray technology as these are important methods providing high-throughput solutions to examine and reveal details about antibody cross-reactivity, as well as they are promising tools for efficient characterization of cross-reactive toxin-targeting antibodies
Summary
Snakebite envenoming was added to the list of the world’s most neglected tropical diseases by the. The current treatment of snakebite envenoming is based on polyclonal antibodies obtained from the plasma of animals hyper-immunized with snake venom [2]. In producing such antivenoms, the snake venoms included in the immunization mixtures (homologous venoms) are chosen based on which snakebites the antivenom is intended to treat. Toxins 2018, 10, 393 of snake toxins are highly variable, which can result in antivenoms with variable neutralizing abilities against certain toxins It is highly desirable for antivenoms to be able to neutralize different toxins in venoms from multiple snake species, a trait called cross-neutralization. The concept of cross-reactivity will be presented and discussed in this review along with a description and discussion of advantages and disadvantages of the different methods used to determine cross-reactivity such as immunodiffusion, immunoblotting, ELISA, enzymatic assays, in vivo neutralization studies, surface plasmon resonance, antivenomics, and high density peptide microarray
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