title: Evaluation of the adjuvant effect of pidotimod on the immune protection induced by UV-attenuated Toxoplasma gondii in mouse models.
abstract: The current anti-Toxoplasma gondii drugs have many shortcomings and effective vaccines against T. gondii may contribute to the control of this pathogen. Pidotimod is a synthetic substance capable of stimulating both cellular and humoral immunity. To investigate the possible adjuvant effect of pidotimod on the immune response to T. gondii in Kunming mice induced by ultraviolet-attenuated T. gondii (UV-T.g), in this study, mice were immunized intraperitoneal (i.p.) with UV-T.g or UV-T.g co-administered with pidotimod (UV-T.g + PT). After infection or challenge by i.p. injection of 10(2) RH tachyzoites, the animal survival rate, parasite burden in peritoneal lavage fluids, liver histopathology, the level of serum anti-toxoplasma IgG antibody, and the mRNA expressions of IL-2, IFN-γ, and TNF-α from spleen analyzed using real-time PCR, were compared among different groups. The results showed that, compared with infected controls, infected mice treated with pidotimod had significantly increased survival rate and extended survival time, decreased parasite burden, improved liver histopathology, increased level of anti-toxoplasma IgG antibody, and increased mRNA expressions of Th1-type cytokine (IL-2, IFN-γ, and TNF-α) (P < 0.01), while mice vaccinated with UV-T.g and then challenged had even significantly increased survival rate and extended survival time, decreased parasite burden, improved liver histopathology, and increased mRNA expressions of Th1-type cytokines (IL-2, IFN-γ, and TNF-α) (P < 0.01); furthermore, vaccinated mice co-administered with pidotimod had even more lower parasite burden, milder liver histopathology, and higher levels of Th1-type cytokine and anti-toxoplasma IgG antibody (P < 0.01). Our data demonstrated that pidotimod in vivo could promote strong and specific humoral and cellular immune response to T. gondii challenge infection when co-administered with UV-attenuated T. gondii. It suggests that pidotimod may have the potential to be used as an effective vaccine adjuvant.
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Shiguang
authors.initials: S
authors.lastname: Huang
authors.forename: Huanqin
authors.initials: H
authors.lastname: Zheng
authors.forename: Yun-quan
authors.initials: YQ
authors.lastname: Li
authors.forename: Zhao-rong
authors.initials: ZR
authors.lastname: Lun
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Lloyd H
authors.initials: LH
authors.lastname: Kasper
authors.forename: Fangli
authors.initials: F
authors.lastname: Lu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D008099:Liver / Q000469:parasitology / Q000473:pathology; D051379:Mice; D015800:Protozoan Proteins / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D053778:Thiazolidines / Q000008:administration & dosage*; D014122:Toxoplasma / Q000276:immunology* / Q000528:radiation effects; D014123:Toxoplasmosis / Q000517:prevention & control*; D014466:Ultraviolet Rays; D014611:Vaccination; D014613:Vaccines, Attenuated
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D053778:Thiazolidines; D014613:Vaccines, Attenuated; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid