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Background/Objectives: Clonorchiasis is a foodborne parasitic disease that can lead to severe biliary fibrosis and cholangiocarcinoma. While praziquantel (PZQ) is available for clonorchiasis treatment, it cannot revert the histopathological damage incurred through parasite-induced fibrosis. Curcumin (CUR) is an emerging experimental drug possessing anti-inflammatory and fibrosis-alleviating effects, thus signifying its potential as an anthelmintic drug. Here, we evaluated the effect of CUR+PZQ combinatorial drug treatment on C. sinensis infection as well as its effect on ameliorating fibrotic tissue damage in rats. Methods: Worm viabilities following CUR and PZQ treatments were confirmed through microscopy and tetrazolium salt absorption. Anthelminthic effect and hepatobiliary damage mitigation in rats were determined by quantifying worm recovery, histopathological staining, and enzyme-linked immunosorbent assay. Results: CUR+PZQ at LD50 doses demonstrated a time- and dose-dependent antiparasitic effect in vitro, which was markedly greater than either drug alone. Rats were infected with C. sinensis, and drugs were administered at 1 and 4 weeks post-infection (wpi) to assess drug-induced changes in worm burden. Significant reductions in worm burden recoveries were observed following CUR+PZQ treatment at both time points, accompanied by markedly reduced serum and mucosal IgG responses. ALT and AST levels were also substantially lower in combinatorial drug treatment groups than controls. Histopathological examinations confirmed that parasite-induced bile duct lumen widening and liver fibrosis were suppressed at 1 wpi, implying that CUR+PZQ co-treatment can alleviate clonorchiasis-associated pathologies. Conclusions: Our findings indicate that CUR+PZQ co-treatment improved parasite clearance and promoted the resolution of hepatobiliary tissue damage resulting from chronic clonorchiasis.

Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in children and the elderly. However, there are no effective antiviral drugs or licensed vaccines available for RSV infection. Here, RSV virus-like particle (VLP) vaccines expressing Pre-F, G, or Pre-F and G proteins on the surface of influenza virus matrix protein 1 (M1) were produced using the baculovirus expression system, and their protective efficacy was evaluated in mice. The morphology and successful assembly of VLPs were confirmed by transmission electron microscope (TEM) and Western blot. High levels of serum IgG antibody response were detected in VLP-immunized mice, and significantly higher levels of IgG2a and IgG2b were found in the Pre-F+G VLP immunization group compared to the unimmunized control. Serum-neutralizing activity was higher in the VLP immunization groups compared to the naïve group, with Pre-F+G VLPs demonstrating superior neutralizing activity to the single antigen-expressing VLP groups. Pulmonary IgA and IgG responses were generally comparable across the immunization groups, with VLPs expressing the Pre-F antigen eliciting higher IFN-γ in spleens. The frequencies of eosinophils and IL-4-producing CD4+ T cell populations were substantially lower in the lungs of VLP-immunized mice, with the PreF+G vaccine inducing a significant increase in CD4+ and CD8+ T cells. VLP immunization significantly decreased the viral titer and inflammation in the lungs of mice, with Pre-F+G VLPs conferring the best protection. In conclusion, our present study suggests that the Pre-F+G VLPs could be a potential vaccine candidate against RSV infection.

Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4+ and CD8+ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.

Rhoptry organelle proteins (ROPs) secreted by Toxoplasma gondii (T. gondii) play a critical role during parasite invasion into host cells. In this study, virus-like particles (VLPs) vaccines containing ROP4 and/or ROP13 together with influenza M1 were generated. ROP4+ROP13 VLPs were produced by combining ROP4 VLPs with ROP13 VLPs, and ROP(4 + 13) VLPs by co-infecting insect cells with recombinant baculovirus expressing ROP4 or ROP13. Mice intranasally immunized with ROP(4 + 13) VLPs showed significantly higher levels of IgG, IgG1, IgG2a and IgA antibody responses in sera compared to ROP4+ROP13VLPs. Upon challenge infection by oral route, mice immunized with ROP(4 + 13) VLPs elicited higher levels of IgG and IgA antibody responses in fecal, urine, intestine and vaginal samples as well as CD4+ T, CD8+ T cells, and germinal center B cell responses compared to other type of vaccines, ROP4 VLPs, ROP13 VLPs, and ROP4+ROP13 VLPs. ROP(4 + 13) VLPs vaccination showed a significant decrease in the size and number of cyst in the brain and less body weight loss compared to combination ROP4+ROP13 VLPs upon challenge infection with T. gondii ME49. These results indicated that the ROP(4 + 13) VLPs vaccination provided enhanced protection against T. gondii infection compared to ROP4+ROP13 VLPs, providing an important insight into vaccine design strategy for T. gondii VLPs vaccines.