Vaccination against the HDL receptor of S. japonicum inhibits egg embryonation and prevents fatal hepatic complication in rabbit model

by Jifeng Zhu, Lina Zhang, Zechao Xue, Zilüe Li, Chun Wang, Fanyan Chen, Yalin Li, Yang Dai, Yonghua Zhou, Sha Zhou, Xiaojun Chen, Kuniko Okumura-Noji, Rui Lu, Shinji Yokoyama, Chuan Su

Schistosomiasis is one of the most important neglected tropical infectious diseases to overcome and the primary cause of its pathogenesis is ectopic maturation of the parasite eggs. Uptake of cholesteryl ester from the host high-density lipoprotein (HDL) is a key in this process in Schistosoma japonicum and CD36-related protein (CD36RP) has been identified as the receptor for this reaction. Antibody against the extracellular domain of CD36RP (Ex160) efficiently blocked the HDL cholesteryl ester uptake and the egg embryonation in vitro. However, whether Ex160 immunization could efficiently raise proper antibody responses to sufficiently block HDL cholesteryl ester uptake and the egg embryonation to protect host in vivo is very interesting but unknown.

In this study, rabbits were immunized with the recombinant Ex160 peptide (rEx160) to evaluate its anti-pathogenic vaccine potential. Immunization with rEx160 induced consistent anti-Ex160 IgG antibody and significant reduction in development of the liver granulomatosis lesions associated with suppressed intrahepatic maturation of the schistosome eggs. The immunization with rEx160 rescued reduction of serum HDL by the infection without changing its size distribution, being consistent with interference of the HDL lipid uptake by the parasites or their eggs by antibody against Ex160 in in vitro culture.

The results demonstrated that vaccination strategy against nutritional supply pathway of the parasite is effective for reducing its pathogenesis.