The immunomodulatory effects of IL-18 against schistosome infection in mice with pVAX1/SjRPS4·CB plasmid vaccination

Abstract

Abstract:

Objective To explore the immunoregulatory effect of pVAX1/IL-18 combined with pVAX1/SjRPS4·CB vaccine against schistosome infection in mice. Methods Seventy female BALB/c mice were divided into 5 groups: the normal saline (NS) group, pVAX1 plasmid group, pVAX1/IL-18 group, pVAX1/SjRPS4·CB group and pVAX1/SjRPS4·CB + pVAX1/IL-18 group. The mice were injected with 100 μg plasmid or an equal volume of NS at the quadriceps femoris of the left hind leg, once every other week, for a total of 3 vaccinations. Three weeks after the final vaccination, blood was collected from the tail, and the levels of IgG, IgG1 and IgG2a were determined by ELISA. The mice were then challenged with 20 ± 1 Schistosoma japonicum cercariae through abdominal patching and sacrificed 8 weeks later. Adult worms of S. japonicum were collected by portal vein perfusion to calculate the worm reduction rate. The liver tissue was collected to calculate the egg reduction rate in hepatic tissues under a microscope. Moreover, spleen was collected at a sterile condition, weighed, and the mouse spleen index was calculated. The splenic lymphocyte proliferation level in vitro was determined using MTT assay. Blood was collected from the tail before infection (at 3 weeks after the final vaccination) and at 2, 4, 6, and 8 weeks after infection, to assess the serum levels of IFN-γ and IL-4 by ELISA. Results At 3 weeks after the final vaccination, the A₄₅₀ values of IgG, IgG1 and IgG2 in the pVAX1/SjRPS4·CB + pVAX1/IL-18 group were 1.03 ± 0.17, 0.32 ± 0.08, and 0.78 ± 0.12, respectively, and the IgG2a/IgG1 ratio was 2.44, all of which were significantly higher than those in the other 4 groups. The worm reduction rate and the egg decrease rate in the pVAX1/SjRPS4·CB + pVAX1/IL-18 group were 52.0% and 63.2%, respectively, both significantly higher than those in the other 3 groups (P < 0.05). The spleen index in the pVAX1/SjRPS4·CB + pVAX1/IL-18 group (3.32 ± 0.37) was also significantly higher than those in the other 4 groups （P < 0.05）. MTT assay showed that the splenic lymphocyte proliferation level in vitro in the pVAX1/SjRPS4·CB + pVAX1/IL-18 group (A₅₇₀ value, 4.45 ± 0.34) was significantly higher than those in the other 4 groups （P < 0.05）. The IFN-γ levels in the pVAX1/SjRPS4·CB + pVAX1/IL-18 group before infection and at 2, 4, 6, and 8 weeks after infection were 569.07 ± 21.15 pg/ml, 560.66 ± 30.84 pg/ml, 577.46 ± 36.45 pg/ml, 605.03 ± 36.91 pg/ml and 636.33 ± 37.35 pg/ml, respectively, all significantly higher than those in the other 4 groups （P < 0.05）. However, the IL-4 level was not altered either before versus after infection, or among different groups （P > 0.05）. Conclusion IL-18 enhances the immunomodulatory effects of pVAX1/SjRPS4·CB against schistosome infection and induces Th1 type immune responses in mice.

Key words: Schistosoma japonica, IL-18, pVAX1/SjRPS4·CB, Vaccine

CLC Number:

R383.24

Hong-bing CHENG, Yun-fei ZHOU, Shu-ju ZHANG, Shi-ping WANG, Qi-mei FENG, Yi-ping LIU, Guo-yan CUI, Hong WEI, Fen LI, Ming-she LIU. The immunomodulatory effects of IL-18 against schistosome infection in mice with pVAX1/SjRPS4·CB plasmid vaccination[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2018, 36(4): 325-330.

Figures/Tables 2

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