title: Protective effect of a DNA vaccine delivered in attenuated Salmonella typhimurium against Toxoplasma gondii infection in mice.
abstract: Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The T. gondii surface antigen protein SAG1 is a significant candidate vaccine against toxoplasmosis. In this study, we evaluated safety, stability of ZJ111/pcDNA3-SAG1, a DNA vaccine delivered in attenuated Salmonella typhimurium, and immune responses induced by immunizing ICR mice orally with ZJ111/pcDNA3-SAG1 of different doses. Mice had no significant differences in body weight between the groups before immunization and at week 4 after the booster immunization. The ZJ111/pcDNA3-SAG1 was eventually eliminated from the spleen and liver on week 6 post-immunization. The plasmid pcDNA3-SAG1 was stably maintained over 90% of the attenuated S. typhimurium population after 100 generations of growth in antibiotic-free media. Oral immunization of mice with ZJ111/pcDNA3-SAG1 elicited specific humoral responses and stimulated proliferation of splenocytes (P<0.05). The cellular immune response was associated with the production of IFN-gamma, indicating that a Th-1 type response was elicited, which was confirmed by the production of large amounts of IgG2a (P<0.01). Mice immunized with ZJ111/pcDNA3-SAG1 displayed significant protection against an intraperitoneally challenge with 500 tachyzoite forms of T. gondii RH strain. Vaccination at 10(7) and 10(8)CFU per mice provided a 20% and 10% survival rate comparing 100% mortality of the non-immunized mice, exhibiting longer living time and better survival rate. These results confirmed a DNA vaccine delivered in attenuated S. typhimurium, ZJ111/pcDNA3-SAG1, can elicit specific immune response as well as provide effective protection against T. gondii infection, and the dosage of 10(7)CFU was a most considerate one.
authors.affiliation: Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang 310029, China.
authors.forename: Daofeng
authors.initials: D
authors.lastname: Qu
authors.forename: Suhua
authors.initials: S
authors.lastname: Wang
authors.forename: Weiming
authors.initials: W
authors.lastname: Cai
authors.forename: Aifang
authors.initials: A
authors.lastname: Du
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D001835:Body Weight; D049109:Cell Proliferation; D015169:Colony Count, Microbial; D005243:Feces / Q000382:microbiology; D005260:Female; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D016019:Survival Analysis; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014123:Toxoplasmosis / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D014774:Virulence
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C047168:SAG1 antigen, Toxoplasma; D019444:Vaccines, DNA; D007371:Interferon-gamma