Assessment of neutralization of Micrurus venoms with a blend of anti-Micrurus tener and anti-ScNtx antibodies

Abstract

Background: Micrurus venoms contain two main groups of toxic protein components: short-chain α-neurotoxins (SNtx) and phospholipases type A₂ (PLA₂). In North America, generally, the Micrurus venoms have low abundance of SNtx compared to that of PLA₂s; however, both are highly toxic to mammals, and consequently both can play a major role in the envenomation processes. Concerning the commercial horse-derived antivenoms against Micrurus from the North America region, they contain a relatively large amount of antibodies against PLA₂s, and a low content of antibodies against short chain α-neurotoxins. This is mainly due to the lower relative abundance of SNtxs, and also to its poor immunogenicity due to their size and nature. Hence, Micrurus antivenoms made in North America usually present low neutralizing capacity towards Micrurus venoms whose lethality depend largely on short chain α-neurotoxins, such as South American Micrurus species.

Methods: Horses were hyperimmunized with either the venom of M. tener (PLA₂-predominant) or a recombinant short-chain consensus α-neurotoxin (ScNtx). Then, the combination of the two monospecific horse antibodies (anti-M. tener and anti-ScNtx) was used to test their efficacy against eleven Micrurus venoms.

Results: The blend of anti-M. tener and anti-ScNtx antibodies had a better capacity to neutralize the lethality of diverse species from North, Central and South American Micrurus venoms. The antibodies combination neutralized both the ScNtx and ten out of eleven Micrurus venom tested, and particularly, it neutralized the venoms of M. distans and M. laticollaris that were neither neutralized by monospecific anti-M. tener nor anti-ScNtx.

Conclusions: These results provide a proof-of-principle for using recombinant immunogens to enrich poor or even non-neutralizing antisera against elapid venoms containing short chain α-neurotoxins to develop antivenoms with higher effectiveness and broader neutralizing capacity.

Keywords: Antivenoms; Coral snakes; Elapid snakes; Micrurus venoms; Phospholipase A(2); Short-chain α-neurotoxin; Snake antivenoms; Snakebites.