Snakebite is a
neglected tropical disease that causes high rates of global mortality and morbidity. Although
snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or
venom-induced
consumption coagulopathy. Despite polyclonal antibody-based
antivenoms being the mainstay life-saving
therapy for
snakebite, they are associated with limited cross-snake species efficacy, as there is often extensive toxin variation between
snake venoms, including those used as immunogens for
antivenom production. This restricts the therapeutic utility of any
antivenom to certain geographical regions. In this study, we explored the feasibility of using recombinantly expressed toxins as immunogens to stimulate focused, pathology-specific,
antibodies in order to broadly counteract specific toxins associated with
snakebite envenoming. Three
snake venom serine proteases (SVSP) toxins, sourced from geographically diverse and medically important viper
snake venoms, were successfully expressed in HEK293F mammalian cells and used for murine immunisation. Analyses of the resulting antibody responses revealed that
ancrod and
RVV-V stimulated the strongest immune responses, and that experimental
antivenoms directed against these recombinant SVSP toxins, and a mixture of the three different immunogens, extensively recognised and exhibited immunological binding towards a variety of native
snake venoms. While the experimental
antivenoms showed some reduction in abnormal clotting parameters stimulated by the toxin immunogens and crude
venom, specifically reducing the depletion of
fibrinogen levels and prolongation of prothrombin times,
fibrinogen degradation experiments revealed that they broadly protected against
venom- and toxin-induced fibrinogenolytic functional activities. Overall, our findings further strengthen the case for the use of recombinant
venom toxins as supplemental immunogens to stimulate focused and desirable antibody responses capable of neutralising
venom-induced pathological effects, and therefore potentially circumventing some of the limitations associated with current
snakebite therapies.