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.

Abstract: A protein, Ancylostoma Secreted Protein (ASP), that is released by hookworm larvae following infection, and which is highly immunogenic in experimental animals, is disclosed. Nucleic acids encoding ASP, antibodies recognizing ASP, and methods of detecting ASP, nucleic acids encoding ASP, and antibodies recognizing ASP, in a sample are also disclosed. ASP is useful in a vaccine for hookworm as well as other soil-transmitted human and veterinary nematodiases. ASP is also useful as a target for specific treatment of hookworm, and can be used in a diagnostic assay for hookworm, using standard protein detection techniques, especially those based on antibodies. DNA encoding ASP is useful both for producing ASP recombinantly and in a diagnostic assay for hookworm. Antibodies recognizing ASP are useful in diagnostic assays to detect protein produced during hookworm infection.

Abstract: A soluble anticoagulant protein isolated and purified from Ancylostoma hookworms markedly prolongs both the prothrombin time and partial thromboplastin time in clotting assays. The protein has an apparent molecular weight of about 6500 daltons and exhibits amino acid sequence homology to the Kunitz-type serine protease inhibitor family. Chromogenic peptide substrate and clotting time assays indicate that the protein inhibits extrinsic pathway clotting factor VIIa, the enzyme responsible for initiating the human coagulation cascade, and factor Xa in the common pathway of the coagulation cascade.