Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice

التفاصيل البيبلوغرافية
العنوان: Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice
المؤلفون: Xue-Zhen Cao, Xing-Quan Zhu, Ting-Ting Li, Qin-Li Liang, Meng-Jie Bai, Jun-Jun He, Jin-Lei Wang, Hany M. Elsheikha
المصدر: The Journal of Immunology. 204:1562-1570
بيانات النشر: The American Association of Immunologists, 2020.
سنة النشر: 2020
مصطلحات موضوعية: Adoptive cell transfer, Fetus, T cell, Immunology, Toxoplasma gondii, Biology, medicine.disease, biology.organism_classification, Virology, Toxoplasmosis, Vaccination, 03 medical and health sciences, Chronic infection, 0302 clinical medicine, medicine.anatomical_structure, parasitic diseases, medicine, Immunology and Allergy, CD8, 030215 immunology
الوصف: In this study, we generated a tkl1 deletion mutant in the Toxoplasma gondii type 1 RH (RHΔtkl1) strain and tested the protective efficacies of vaccination using RHΔtkl1 tachyzoites against acute, chronic, and congenital T. gondii infections in Kunming mice. Mice vaccinated with RHΔtkl1 mounted a strong humoral and cellular response as shown by elevated levels of anti–T. gondii–specific IgG, IL-2, IL-12, IFN-γ, and IL-10. All RHΔtkl1-vaccinated mice survived a lethal challenge with 1 × 103 tachyzoites of type 1 RH or ToxoDB#9 (PYS or TgC7) strain as well as 100 cysts or oocysts of Prugniuad strain. All mock-vaccinated plus infected mice have died. Vaccination also protected against cyst- or oocyst-caused chronic infection, reduced vertical transmission caused by oocysts, increased litter size, and maintained body weight of pups born to dams challenged with 10 oocysts on day 5 of gestation. In contrast, all mock-vaccinated plus oocysts-infected dams had aborted, and no fetus has survived. Vaccinated dams remained healthy postinfection, and their brain cyst burden was significantly reduced compared with mock-vaccinated dams infected with oocysts. In vivo depletion of CD4+ T cells, CD8+ T cells, and B cells revealed that CD8+ T cells are involved in the protection of mice against T. gondii infection. Additionally, adoptive transfer of CD8+ T cells from RHΔtkl1-vaccinated mice significantly enhanced the survival of naive mice infected with the pathogenic strain. Together, these data reaffirm the importance of CD8+ T cell responses in future vaccine design for toxoplasmosis and present T. gondii tkl1 gene as a promising vaccine candidate.
تدمد: 1550-6606
0022-1767
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::aa4e80314fe7688453fad215760ffd8aTest
https://doi.org/10.4049/jimmunol.1900410Test
حقوق: OPEN
رقم الانضمام: edsair.doi...........aa4e80314fe7688453fad215760ffd8a
قاعدة البيانات: OpenAIRE