Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase

Abstract

Alveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis Leucine aminopeptidase (EM-LAP) induced specific immune response and had an inhibiting effect on the parasites. In this study, the therapeutic effect of recombinant EM-LAP (rEM-LAP) on AE was evaluated and verified using Ubenimex, a broad-spectrum inhibitor of LAP. The results reveal that rEM-LAP could inhibit cyst growth and invasion and induce specific immunity response in BALB/c mice infected with E. multilocularis protoscoleces. The ultrasonic, MRI, and morphological results show that treatment with rEM-LAP inhibits E. multilocularis infection and reduces cyst weight, number, fibrosis and invasion. The same effect is observed for the treatment with Ubenimex by inhibiting LAP activity. The indirect ELISA shows that rEM-LAP could induce specific immunity response and produce high levels of IgG, IgG1, IgG2a, IgM, and IgA, and the serum levels of IFN-γ and IL-4 are significantly increased compared to the control groups, indicating that treatment with rEM-LAP leads to a Th1 and Th2 mixed-type immune response. This study suggests that EM-LAP could be a potential therapeutic target of E. multilocularis infection.

Ubenimex combined with Albendazole for the treatment of Echinococcus multilocularis-induced alveolar echinococcosis in mice

“…We have previously found that vaccination with EM-LAP induced specific immune response and inhibited the invasion of E. multilocularis (7). We have also evaluated the therapeutic effect of recombinant EM-LAP (rEM-LAP) on AE and found that Ubenimex, a broad-spectrum inhibitor of LAP, also showed similar inhibitory effect on the invasion of E. multilocularis (8). These studies suggest that EM-LAP could be a potential therapeutic target of E. multilocularis infection.…”

“…All animal experiments were performed in compliance with the regulations of the Ministry of Science and Technology of China and approved by the Experimental Committee of Qinghai University (QHDX-2019-09). Male BALB/c specific pathogen free (SPF) mice of 6-8 weeks old were purchased from Beijing Spaefer Biotechnology Company (SCXK2019-0010) and fed with sterilized feed and water over a 24 h day/night cycle in an animal biosafety level II (ABSL-2) laboratory (7,8,31). All mice were intraperitoneally injected with 2,000 protoscoleces, which were isolated from Gerbillinae infected with E. multilocularis for over 20 weeks in the Research Center for High Altitude Medicine (7,32).…”

“…E. multilocularis metacestodes and cysts can invade the vasculature, resulting in metastases to other liver lobes and even other tissues and organs. E. multilocularis can also lead to liver fibrosis through E. multilocularis Leucine aminopeptidase (EM-LAP) (7,8). Existing drugs like Albendazole have lower water solubility and drug concentration in hydatid lesions, making it difficult to completely clear all parasites and restrain infiltrative growth (9).…”

Current status and future prospects of Echinococcus multilocularis vaccine candidates: A systematic review

“… rEM-LAP could induce specific immunity response and produce high levels of IgG, IgG1, IgG2a, IgM, and IgA, and the serum levels of IFN-γ and IL-4 are significantly increased compared to the control groups, indicating that treatment with rEM-LAP leads to a Th1 and Th2 mixed-type immune response. 10 ( Zhou et al, 2022 ) LTB-ETBM CFA IFA CpG 0.5 mg/mL BALB/c 1000 protoscoleces (i.p.) The LTB-ETBM significantly inhibited the formation of cysts in mice challenged with 1000 E.m. protoscoleces.…”

“…Moreover, it induces a specific immune response in BALB/c mice infected with E. multilocularis. Also, treatment with rEM-LAP reduces weight, number, fibrosis, and invasion; it also results in high levels of IgG, IgG1, IgG2a, IgM, IgA, IFN-γ, and IL-4 ( Zhou et al, 2022 ). LTB-EMY162 helped treat and stop E. multilocularis , but it didn't completely protect ( Li et al, 2018 ).…”