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

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.

Preclinical Assessment of a New Polyvalent Antivenom (Inoserp Europe) against Several Species of the Subfamily Viperinae.

The European continent is inhabited by medically important venomous Viperinae snakes. Vipera ammodytes, Vipera berus, and Vipera aspis cause the greatest public health problems in Europe, but there are other equally significant snakes in specific regions of the continent. Immunotherapy is indicated for patients with systemic envenoming, of which there are approximately 4000 annual cases in Europe, and was suggested as an indication for young children and pregnant women, even if they do not have systemic symptoms. In the present study, the safety and venom-neutralizing efficacy of Inoserp Europe-a new F(ab')2 polyvalent antivenom, designed to treat envenoming by snakes in the Eurasian region-were evaluated. In accordance with World Health Organization recommendations, several quality control parameters were applied to evaluate the safety of this antivenom. The venom-neutralizing efficacy of the antivenom was evaluated in mice and the results showed it had appropriate neutralizing potency against the venoms of several species of Vipera, Montivipera, and Macrovipera. Paraspecificity of the antivenom was demonstrated as well, since it neutralized venoms of species not included in the immunization schemes and contains satisfactory levels of total proteins and F(ab')2 fragment concentration. Therefore, this new polyvalent antivenom could be effective in the treatment of snake envenoming in Europe, including Western Russia and Turkey.