Protective immunity induced by a DNA vaccine expressing eIF4A of Toxoplasma gondii against acute toxoplasmosis in mice.
Toxoplasma gondii is an obligate intracellular protozoan parasite infecting humans, mammals and birds. Eukaryotic translation initiation factor (eIF4A) is a newly identified protein associated with tachyzoite virulence. To evaluate the protective efficacy of T. gondii eIF4A, a DNA vaccine (pVAX-eIF4A) encoding T. gondii eIF4A (Tg-eIF4A) gene was constructed. The expression ability of this recombinant DNA plasmid was examined in Marc145 cells by IFA. Then, Kunming mice were intramuscularly immunized with pVAX-eIF4A and followed by challenge infection with the highly virulent T. gondii RH strain. The results showed that vaccination with pVAX-eIF4A elicited specific humoral responses, with high IgG antibody titers and specific lymphocyte proliferative responses. The cellular immune response was associated with significant production of IFN-γ, IL-2 in Kunming mice, and a mixed IgG1/IgG2a response with predominance of IgG2a production, indicating that a Th1 type response was elicited after immunization with pVAX-eIF4A. In addition, the increase of the percentage of CD8+ T cells in lymphoid in mice suggested the activation of MHC class I restricted antigen presentation pathways. After lethal challenge, the mice vaccinated with the pVAX-eIF4A showed a significantly prolonged survival time (23.0±5.5 days) compared with control mice which died within 7 days of challenge (P<0.05). These results demonstrate that pVAX-eIF4A could elicit strong humoral, Th1-type cellular immune responses and increase survival time of immunized mice, suggesting that eIF4A is a promising vaccine candidate against acute T. gondii infection in mice.
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China.
Jia
J
Chen
Si-Yang
SY
Huang
Zhong-Yuan
ZY
Li
Zi-Guo
ZG
Yuan
Dong-Hui
DH
Zhou
Eskild
E
Petersen
Nian-Zhang
NZ
Zhang
Xing-Quan
XQ
Zhu
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D007376:Interleukin-2; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D039601:Eukaryotic Initiation Factor-4A