Abstract: The present disclosure generally relates to genetic methods of manipulating helminths, e.g., hookworms, to act as a biological delivery vehicle for therapeutic polypeptides in mammals. Furthermore, the disclosure is drawn to compositions comprising genetically modified hookworms and methods of use, including the administration of the helminths to one or more mammals to provide a continuous supply of a synthetic or modified polypeptide (e.g., HIV neutralizing antibodies) which may mitigate infection and/or infection intensity, otherwise resulting in an increase in a desirable phenotypic trait.