标题：Immunogenic multistage recombinant protein vaccine confers partial protection against experimental toxoplasmosis mimicking natural infection in murine model
摘要：Toxoplasma gondii is a protozoan parasite that can infect warm-blooded animals including humans. Vaccination studies mostly use tachyzoite specific proteins however in natural route of infection, toxoplasmosis initiates with tissue cysts (bradyzoites) or oocysts (sporozoites) and thereafter stage conversion takes place where the tachyzoites take action and cause acute infection continues with tachyzoites. Despite this knowledge, challenging models used in the vaccination studies prefer administration of tissue cyst forming strains intraperitoneally or subcutaneously instead of oral administration which is the natural route of infection. In the present study, a multivalent adjuvanted recombinant protein vaccine that contains bradyzoite specific BAG1 and tachyzoite specific GRA1 protein and controls were administered to female Swiss Webster outbred mice. Humoral and cellular immune responses were analyzed by Rec-ELISA, Western blot, and flow cytometry. Mice were infected orally with T. gondii PRU strain tissue cysts using feeding needle to mimic the natural route of infection. 40days after challenging microscopy and Real Time PCR were performed to determine the protection level. Analysis of sera obtained from vaccinated mice showed strong anti-BAG1 and anti-GRA1 IgG responses. The IgG2a response was significantly higher (P<0.0001) and the ratio of CD8+T lymphocytes secreting IFN-@c almost doubled compared to PBS control which are indicative of protection against toxoplasmosis. The amount of tissue cysts in vaccinated group was reduced 10.5% compared to control group. To generate a protective vaccine against toxoplasmosis, multistage vaccines and usage of challenging models mimicking natural route of infection are critical cornerstones. In this study, we generated a BAG1 and GRA1 multistage vaccine that induced strong immune response in which the protection was not at anticipated level. In addition, the murine model was orally challenged with tissue cysts to mimic natural route of infection.
关键词：Toxoplasma gondii
; Recombinant protein vaccine
; BAG1
; GRA1
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