Abstract
Papain, an experimental model protease, was used to decipher the protective mechanism(s) of the cysteine peptidase-based schistosomiasis vaccine. To examine the role of T lymphocytes, athymic nude (nu/nu) and immunocompetent haired (nu/+) mice were subcutaneously (sc) injected with 50 µg active papain two days before percutaneous exposure to 100 cercariae of Schistosoma mansoni. Highly significant (P < 0.005) reductions in worm burden required competent T lymphocytes, while significant increases (P < 0.05) of >80% in dead parasite ova in the small intestine were independent of T cell activity and likely relied on the innate immune axis. To investigate the role of enzymatic activity, immunocompetent mice were sc injected with 50 µg active or E-64-inactivated papain two days before exposure to cercariae. The reductions in worm burden were highly significant (P < 0.0001), reaching >65% and 40% in active and inactivated papain-treated mice, respectively. Similar highly significant (P < 0.0001) decreases of 85% in the viability of parasite ova in the small intestine occurred in both active and inactivated papain-treated mice. These findings indicated that immune responses elicited by one or more papain structural motifs are necessary and sufficient for induction of considerable parasite and egg attrition. Correlates of protection included IgG1-dominated antibody responses and increases in the levels of uric acid and arachidonic acid in the lung and liver upon parasite migration in these sites. Identification of the shared patterns or motifs in cysteine peptidases and evaluation of their immune protective potential will pave the way to the development of a safe, efficacious, storage-stable, and cost-effective schistosomiasis vaccine.