Bothrops jararacussu Venom Inactivated by High Hydrostatic Pressure Enhances the Immunogenicity Response in Horses and Triggers Unexpected Cross-Reactivity with Other Snake Venoms

High hydrostatic pressure (HHP) has been used for viral inactivation to facilitate vaccine development when immunogenicity is maintained or even increased. In this work, we used HHP to inactivate <i>Bothrops jararacussu</i> venom. Our protocol promotes the loss of or decrease in many biological activities in venom. Horses were immunized with pressurized venom, and in contrast to native venom, this procedure does not induce any damage to animals. Furthermore, the serum obtained with pressurized venom efficiently neutralized all biological activities of <i>B. jararacussu</i> venom. Antibody titrations were higher in serum produced with pressurized venom compared to that produced by native venom, and this antivenom was not only effective against the venom of <i>B. jararacussu</i> but against the venom of other species and genera. In conclusion, our data show a new technique for producing hyperimmune serum using venom inactivated by HHP, and this method is associated with a reduction in toxic effects in immunized animals and higher potency.