title: Dose-dependent establishment of Trichuris suis larvae in Göttingen minipigs.
abstract: Embryonated eggs of the pig whipworm Trichuris suis (TSOee) constitute the active pharmaceutical ingredient (API) in a medicinal product explored in human clinical trials against several immune-mediated diseases. The measurement of TSO biological potency (hatchability and infectivity) is a requirement for the assessment of TSO's pharmacological potency in human clinical trials. The present study aims to validate the dose-dependent establishment of T. suis larvae in Göttingen minipigs and eventual clinical implication of a dose range (1000-10,000 TSO). Four groups of 5 minipigs were inoculated with doses of 1000, 2500, 7500, and 10,000 TSOee, respectively, to evaluate a range of concentrations of TSOee in a minipig infectivity model. Unembryonated eggs (TSOue) were added to keep the total egg number in the inoculum constant at 10,000 eggs. Two groups received 2500 and 7500 TSOee per pig without the addition of TSOue as controls. The intestinal larval establishment at 21 days post inoculation (dpi) demonstrated a clear positive linear dose-response relationship between numbers of inoculated TSOee and recovered larvae. There was a low level of variation in larval counts in all study groups. Thus, the infectivity model in minipigs within the tested dose range offers a reliable, sensitive and accurate assay for testing biological potency of TSO.
authors.affiliation: Section for Organismal Biology, Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark. Electronic address: nerminav@plen.ku.dk.
authors.forename: Nermina
authors.initials: N
authors.lastname: Vejzagić
authors.affiliation: Parasite Technologies A/S, Dr. Neergaards Vej 3, 2970 Hørsholm, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Roepstorff
authors.affiliation: Parasite Technologies A/S, Dr. Neergaards Vej 3, 2970 Hørsholm, Denmark.
authors.forename: Helene
authors.initials: H
authors.lastname: Kringel
authors.affiliation: Parasite Technologies A/S, Dr. Neergaards Vej 3, 2970 Hørsholm, Denmark; Parasitology and Aquatic Diseases, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 100, 1870 Frederiksberg C, Denmark.
authors.forename: Stig Milan
authors.initials: SM
authors.lastname: Thamsborg
authors.affiliation: Parasite Technologies A/S, Dr. Neergaards Vej 3, 2970 Hørsholm, Denmark.
authors.forename: Mads Pårup
authors.initials: MP
authors.lastname: Nielsen
authors.affiliation: Section for Organismal Biology, Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark; Parasite Technologies A/S, Dr. Neergaards Vej 3, 2970 Hørsholm, Denmark.
authors.forename: Christian M O
authors.initials: CM
authors.lastname: Kapel
mesh_terms: D000818:Animals; D005260:Female; D013552:Swine; D013553:Swine Diseases / Q000469:parasitology*; D013556:Swine, Miniature / Q000469:parasitology*; D014257:Trichuriasis / Q000469:parasitology / Q000662:veterinary*; D014258:Trichuris / Q000502:physiology*
keywords: Dose–response; Embryonated eggs; Göttingen minipigs; Inoculation doses; TSO; Trichuris suis