National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, Jiangsu, China.
Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
PLoS Negl Trop Dis. 2023 Nov 29;17(11):e0011749. doi: 10.1371/journal.pntd.0011749. eCollection 2023 Nov.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: The results demonstrated that vaccination strategy against nutritional supply pathway of the parasite is effective for reducing its pathogenesis.
血吸虫病是最需要克服的重要被忽视热带传染病之一，其发病机制的主要原因是寄生虫卵的异位成熟。从宿主高密度脂蛋白（HDL）摄取胆固醇酯是日本血吸虫（Schistosoma japonicum）这一过程中的关键，已经确定 CD36 相关蛋白（CD36RP）是该反应的受体。针对 CD36RP 细胞外结构域的抗体（Ex160）有效地阻断了 HDL 胆固醇酯的摄取和体外卵的胚胎发生。然而，Ex160 免疫是否能有效地产生适当的抗体反应，以充分阻断 HDL 胆固醇酯的摄取和卵的胚胎发生，从而在体内保护宿主，这是非常有趣但未知的。
方法/主要发现：在这项研究中，用重组 Ex160 肽（rEx160）免疫兔，以评估其作为抗病原疫苗的潜力。rEx160 免疫诱导一致的抗 Ex160 IgG 抗体，并显著减少与肝内血吸虫卵成熟抑制相关的肝肉芽肿病变的发展。rEx160 免疫接种挽救了感染引起的血清 HDL 减少，而不改变其大小分布，这与抗体在体外培养中对寄生虫或其卵摄取 HDL 脂质的干扰一致。
结论/意义：结果表明，针对寄生虫营养供应途径的疫苗接种策略可有效降低其发病机制。
