期刊
JOURNAL OF INFECTIOUS DISEASES
卷 218, 期 5, 页码 768-777出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiy211
关键词
Toxoplasma gondii; vaccination; Ca2+-dependent protein kinase 2; attenuated vaccine; protective immunity
资金
- National Natural Science Foundation of China [31472184, 31230073]
- Natural Science Foundation of Gansu Province for Distinguished Young Scholars [1506RJDA133]
- National Key Research and Development Program of China [2017YFD0501304]
- Elite Program of Chinese Academy of Agricultural Sciences
Background. The threat of Toxoplasma gondii infection in immunocompromised individuals and pregnant women necessitates the development of a safe and effective vaccine. Here, we examined the immune protection conferred by a live attenuated strain of T. gondii. Methods. We tested the efficacy of intraperitoneal vaccination using 500 Ca2+-dependent protein kinase 2 (cdpk2)-deficient tachyzoites of T. gondii Pru strain against acute, chronic, and congenital toxoplasmosis in mice. The kinetics of antibody response, cytokines, and other quantifiable correlates of protection against T. gondii infection were determined. Results. Vaccination with Pru:Delta cdpk2 induced a high level of anti-T. gondii immunoglobulin G titer, type 1 T-helper (Th1) response at 28 days postvaccination, and a mixed Th1/type 2 T-helper response at 70 days postvaccination. All vaccinated mice survived a heterologous challenge with 1000 tachyzoites of RH or ToxoDB#9 (PYS or TgC7) strains. Also, vaccination protected against homologous infection with 20 T. gondii Pru cysts, and improved pregnancy outcome by reducing parasite cyst load in the brain, maintaining litter size and body weight of pups born to vaccinated dams challenged with 10 Pru cysts compared to pups born to unvaccinated dams. Conclusions. The use of T. gondii Pru:Delta cdpk2 mutant strain represents a promising approach to protection against acute, chronic, and congenital toxoplasmosis in mice.
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