A Taenia saginata oncosphere-derived adhesion protein (HP6) with surface and secreted localization was used to successfully vaccinate calves against oral challenge with T. saginata eggs. In contrast, vaccination using a combination of T. saginata oncosphere-derived peptides, selected on the basis of their antigenic index, and including three derived from the HP6 molecule (HP6-1, HP6-2 and HP6-3), was unsuccessful. This either indicated that the wrong peptides were selected or, in the case of the HP6 protein, that the protective epitope is conformational in nature. The protection experiments were monitored using a parasite antigen detection ELISA (HP10 Ag-ELISA), which allowed the early determination of the success of the vaccination protocol, subsequently confirmed at autopsy. PCR assays were used for the first time to confirm the presence of T. saginata DNA in lesions recovered at autopsy and thus verify the parasite origin of the lesions.