An inactivated bacterium (paraprobiotic) expressing Cry5B as a therapeutic for and spp. infections in large animals.

and are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, , is passed from humans to pigs and . The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Cry5B protein with known anthelmintic properties, against zoonotic and spp. This paraprobiotic, known as IBaCC, intoxicated larvae and was highly effective against intestinal infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in -infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world.