Guiding recombinant antivenom development by omics technologies

Abstract

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In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

“…Taken together, the data provided here constitutes a proof of concept for the use of oligoclonal mixtures of recombinant human IgGs against snakebite envenoming. The use of carefully selected human IgG antibodies holds the promise of delivering safer and more effective treatments against snakebite envenoming due to the compatibility with the human immune system and the possibility of only including antibodies of therapeutic value in a recombinant antivenom 5 , 6 . Moreover, as cost-efficacy remains one of the main challenges of delivering biotherapeutics to patients in developing countries 1 , the use of oligoclonal recombinantly expressed human IgGs has been theorized to be cost-competitive with current plasma-derived antivenoms 13 .…”

“…Antivenoms derived from the plasma of hyper-immunized animals remain the mainstay of snakebite envenoming therapy 3 . However, these present a range of drawbacks due to their relatively high cost and their heterologous nature that causes, in some patients, a number of side effects, such as serum sickness and early adverse reactions, which may include severe anaphylaxis 4 – 6 . Furthermore, it is estimated that only a fraction of the antibodies in most current antivenoms have a therapeutic value, as the majority of antibodies isolated from animal plasma are directed against antigens that are either unrelated to snake venom or related to venom components with negligible contribution to venom toxicity 5 .…”

Antibody Cross-Reactivity in Antivenom Research

“…With the introduction of powerful mass spectrometry approaches in venom research, novel methodologies have emerged, which facilitate more holistic and high-throughput assessments of cross-reactivity of toxin-targeting antibodies [ 11 , 54 ], which may limit the use of rodent assays [ 55 ]. Antivenomics is a proteomics-based approach [ 56 ] designed to support in vivo and in vitro preclinical tests [ 57 , 58 ] in the qualitative and quantitative characterization of the immunological profile and the extent of cross-reactivity of antivenoms towards venoms [ 55 ].…”

Recent Advances in Next Generation Snakebite Antivenoms

“…Antivenoms were first envisioned in their current form by A. Calmette and C. Phisalix in 1894 [15]. Despite recent reports on innovative approaches for developing a new generation of antivenoms based on biotechnological methods, medicinal chemistry, and antibody technologies [16][17][18], plasmaderived antivenoms of animal origin remain the only effective treatment against snakebite envenoming [19,20]. Due to its severity, the World Health Organisation (WHO) recently reinstated snakebite envenoming on its list of Neglected Tropical Diseases [21] and set down a working group that will develop an official strategy for prevention and treatment of snakebite envenoming (http://www.who.int/snakebites/control/WHO_Working_Group_on_Snakebite_Envenoming/en/).…”