For over a century, polyclonal
antibodies have been used to treat
snakebite envenoming and are still considered by the WHO as the only scientifically validated treatment for
snakebites. Nevertheless, moderate innovations have been introduced to this
immunotherapy. New strategies and approaches to understanding how
antibodies recognize and neutralize
snake toxins represent a challenge for next-generation
antivenoms. The neurotoxic activity of
Micrurus venom is mainly due to two distinct
protein families,
three-finger toxins (3FTx) and
phospholipases A2 (PLA2). Structural conservation among
protein family members may represent an opportunity to generate neutralizing
monoclonal antibodies (mAbs) against family-conserved
epitopes. In this work, we sought to produce a set of
monoclonal antibodies against the most toxic components of M. altirostris
venom. To this end, the crude
venom was fractionated, and its major toxic
proteins were identified and used to generate a panel of five mAbs. The specificity of these mAbs was characterized by ELISA and antivenomics approaches. Two of the generated mAbs recognized PLA2
epitopes. They inhibited PLA2 catalytic activity and showed paraspecific neutralization against the
myotoxicity from the lethal effect of Micrurus and
Naja venoms' PLA2s.
Epitope conservation among
venom PLA2 molecules suggests the possibility of generating pan-PLA2
neutralizing antibodies.