A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp.

Abstract

Accidents involving Micrurus snakes are not the most common ones but are noteworthy due to their severity. Victims envenomed by Micrurus snakes are at high risk of death and therefore must be treated with coral antivenom. In Brazil, the immunization mixture used to fabricate coral antivenom contains Micrurus frontalis and Micrurus corallinus venoms, which are difficult to be obtained in adequate amounts. Different approaches to solve the venom limitation problem have been attempted, including the use of synthetic and recombinant antigens as substitutes. The present work proposes a combined immunization protocol, using priming doses of M. frontalis venom and booster doses of synthetic B-cell epitopes derived from M. corallinus toxins (four three-finger toxins-3FTX; and one phospholipase A2-PLA2) to obtain coral antivenom in a rabbit model. Immunized animals elicited a humoral response against both M. frontalis and M. corallinus venoms, as detected by sera reactivity in ELISA and Western Blot. Relevant cross-reactivity of the obtained sera with other Micrurus species (Micrurus altirostris, Micrurus lemniscatus, Micrurus spixii, Micrurus surinamensis) venoms was also observed. The elicited antibodies were able to neutralize PLA2 activity of both M. frontalis and M. corallinus venoms. In vivo, immunized rabbit sera completely protected mice from a challenge with 1.5 median lethal dose (LD50) of M. corallinus venom and 50% of mice challenged with 1.5 LD50 of M. frontalis venom. These results show that this combined protocol may be a suitable alternative to reduce the amount of venom used in coral antivenom production in Brazil.

Computer-Aided Analysis of West Sub-Saharan Africa Snakes Venom towards the Design of Epitope-Based Poly-Specific Antivenoms

“…A closer inspection of other predicted epitopes revealed that some short motifs within them are indeed part of other already validated epitopes. For instance, it is interesting to find that motif ATCP, present in the predicted epitopes ATCPKPTNVRETI and AATCPKVK that cover Dendroaspis species and which have been predicted through 3D features, has been found in validated 3FTXs epitopes from the Asian Bungarus multicinctus and the American Micrurus corallinus [36,37]. Nonetheless, a limitation of the study is that most of the epitope sequences identified were predicted and yet await experimental validation of their biological function.…”

First Insights into the Venom Composition of Two Ecuadorian Coral Snakes

“…They are considered ideal organisms for ecological, evolutionary, pharmacological, physiological, phylogenetic, and proteomic studies [ 29 ]. Their ability to produce small quantities of venoms has limited the manufacturing of antivenoms as well as structural, functional, and immunological research [ 35 ]. The first integrative venom proteomics using coral snake was developed in 2008 [ 36 ], but most of the quantitative estimation of proteome compositions were published in the last 10 years [ 27 , 30 ].…”

Myalgia as a Symptom of Envenomation by the Eastern Coral Snake, Micrurus Fulvius: A Case Report

“…Efforts to develop a combined antivenin to Micrurus species are underway in South America, where Micrurus species diversity is greater. 38,39 As NACSA is prone to periods of shortages lasting several years, a combined Micrurus antivenin might be investigated for use in M fulvius envenomations in the future. Research is also underway to develop a more efficient method of producing antivenin for the South American species Micrurus corallinus using genetic immunization with a synthetic multiepitope gene followed by booster doses with recombinant protein.…”