Comparing Traditional and Toxin-Oriented Approaches towards Antivenom Production against Bitis arietans Snake Venom

Accidents with snakes are responsible for about 32,000 deaths annually in sub-Saharan Africa, caused mostly by snakes from the genus Bitis, in particular Bitis arietans. B. arietans venom is composed of a complex mixture of toxins, mainly metalloproteases, serine proteases, phospholipases, lectins, and disintegrins. In this work, we compared two approaches to anti-B. arietans antivenom production: immunization with crude snake venom (traditional approach) and immunization with selected key toxins isolated from the snake venom (toxin oriented approach). Fractions from B. arietans venom were isolated by size exclusion chromatography. Crude venom and samples containing serine proteases or metalloproteases were selected for the immunization of BALB/c mice. Anti-B. arietans and anti-serine proteases plasmas showed a similar recognition profile and higher titers and affinity than the anti-metalloproteases plasma. Cross-recognition of other Bitis venoms was observed, but with low intensity. Although the plasma of all experimental groups inhibited the enzymatic activity of B. arietans venom in vitro, in vivo protection was not achieved. Our results have shown limitations in both approaches considered. Based on this, we proposed a model of polyclonal, species-specific, monovalent antivenoms that could be used as a base to produce customizable polyvalent sera for use in sub-Saharan Africa.

Automated summary

Accidents with snakes in sub-Saharan Africa cause about 32,000 deaths annually, primarily due to snakes from the Bitis genus, particularly Bitis arietans. The venom of B. arietans contains a complex mixture of toxins, mostly metalloproteases, serine proteases, phospholipases, lectins, and disintegrins. This study compared two approaches for producing anti-B. arietans antivenom - immunization with crude snake venom and immunization with selected key toxins from the venom. The results showed limitations in both approaches and proposed a model for customizable polyvalent sera in sub-Saharan Africa.