Oral immunotherapy with anti-ES24 antibodies reduces burden and fecundity of Haemonchus contortus and inflammation in lambs artificially infected

Increasing multiple anthelmintic resistance in Haemonchus contortus has been reported worldwide, highlighting the need for alternative strategies to mitigate the damage caused by this nematode. In this study, we developed and evaluated an immunotherapy protocol based on specific antibodies against the ES24 antigen of H. contortus. Purified and biologically active immunoglobulins were successfully produced through the immunization of sheep donors. The purified immunoglobulins were pooled, evaluated for specific anti-ES24 levels of IgG, IgM and IgA isotypes by indirect ELISA, presenting reduced larval infectivity in vitro. In vivo, immunotherapy-treated lambs showed reduced worm development and fecundity following experimental H. contortus infection. Immunotherapy administration also significantly reduced inflammatory responses, as demonstrated by lower peripheral monocyte counts and reduced neutrophilic infiltration in the abomasal lamina propria compared to untreated infected lambs. Furthermore, treated lambs exhibited enhanced innate and adaptive immune responses, characterized locally by increased expression of TLR4 and GAL11, and systemically by lymphocytosis, particularly in female lambs. Overall, the proposed immunotherapy protocol represents a promising immunotherapy to reduce the impact of haemonchosis on sheep production, targeting antigens with low probability of developing resistance.