Protective effect of DNA-mediated immunization with liposome-encapsulated GRA4 against infection of Toxoplasma gondii |
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Authors: | Rui Chen Shao-hong Lu Qun-bo Tong Di Lou Dong-yan Shi Bing-bing Jia Guo-ping Huang Jin-fu Wang |
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Institution: | (1) College of Life Sciences, Zhejiang University, Hangzhou, 310058, China;(2) Institute of Parasitology, Zhejiang Academy of Medical Science, Hangzhou, 310013, China |
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Abstract: | The dense granule protein 4 (GRA4) is a granular protein from Toxoplasma gondii, and is a candidate for vaccination against this parasite. In this study, the plasmid pcDNA3.1-GRA4 (pGRA4), encoding for
the GRA4 antigen, was incorporated by the dehydration-rehydration method into liposomes composed of 16 mmol/L egg phosphatidylcholine
(PC), 8 mmol/L dioleoyl phosphatidylethanolamine (DOPE), and 4 mmol/L 1,2-diodeoyl-3-(trimethylammonium) propane (DOTAP).
C57BL/6 mice and BALB/c mice were immunized intramuscularly three times with liposome-encapsulated pGRA4 to determine whether
DNA immunization could elicit a protective immune response to T. gondii. Enzyme-linked immunosorbent assay (ELISA) of sera from immunized mice showed that liposome-encapsulated pGRA4 generated
high levels of IgG antibodies to GRA4. Production of primary interferon (IFN)-γ and interleukin (IL)-2 in GRA4-stimulated
splenocytes from vaccinated mice suggested a modulated Th1-type response. 72.7% of C57BL/6 mice immunized with liposome-encapsulated
pGRA4 survived the challenge with 80 tissue cysts of ME49 strain, whereas C57BL/6 mice immunized with pGRA4 had only a survival
rate of 54.5%. When immunized BALB/c mice were intraperitoneally challenged with 103 tachyzoites of the highly virulent RH strain, the survival time of mice immunized with liposome-encapsulated pGRA4 was markedly
longer than that of other groups. Our observations show that liposome-encapsulated pGRA4 enhanced the protective effect against
infection of T. gondii.
Project supported by the Science Foundation of the Health Bureau of Zhejiang Province, China (Nos. 2003QN003 and 2005A001)
and the Science Foundation of the Science and Technology Department of Zhejiang Province, China (No. 2006C13022) |
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Keywords: | DNA vaccine Granule protein 4 (GRA4) Liposome Toxoplasma gondii |
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