Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis

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 live-attenuated strain of T. gondii. Methods: We tested the efficacy of intra...

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Main Authors: Wang, Jin-Lei, Li, Ting-Ting, Elsheikha, Hany M., Chen, Kai, Cong, Wei, Yang, Wen-Bin, Bai, Meng-Jie, Huang, Si-Yang, Zhu, Xing-Quan
Format: Article
Language:English
Published: Oxford University Press 2018
Subjects:
Online Access:https://eprints.nottingham.ac.uk/51324/
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author Wang, Jin-Lei
Li, Ting-Ting
Elsheikha, Hany M.
Chen, Kai
Cong, Wei
Yang, Wen-Bin
Bai, Meng-Jie
Huang, Si-Yang
Zhu, Xing-Quan
author_facet Wang, Jin-Lei
Li, Ting-Ting
Elsheikha, Hany M.
Chen, Kai
Cong, Wei
Yang, Wen-Bin
Bai, Meng-Jie
Huang, Si-Yang
Zhu, Xing-Quan
author_sort Wang, Jin-Lei
building Nottingham Research Data Repository
collection Online Access
description 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 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:Δcdpk2 induced a high level of anti-T. gondii IgG titer, Th1 response at 28 days post-vaccination (dpv), and mixed Th1/Th2 response at 70 dpv. 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. Conclusion: The use of T. gondii Pru:Δcdpk2 mutant strain represents a promising approach to protection against acute, chronic and congenital toxoplasmosis in mice.
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spelling nottingham-513242019-04-13T04:30:16Z https://eprints.nottingham.ac.uk/51324/ Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis Wang, Jin-Lei Li, Ting-Ting Elsheikha, Hany M. Chen, Kai Cong, Wei Yang, Wen-Bin Bai, Meng-Jie Huang, Si-Yang Zhu, Xing-Quan 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 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:Δcdpk2 induced a high level of anti-T. gondii IgG titer, Th1 response at 28 days post-vaccination (dpv), and mixed Th1/Th2 response at 70 dpv. 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. Conclusion: The use of T. gondii Pru:Δcdpk2 mutant strain represents a promising approach to protection against acute, chronic and congenital toxoplasmosis in mice. Oxford University Press 2018-04-13 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/51324/1/jiy211-accepted%20manuscript.pdf Wang, Jin-Lei, Li, Ting-Ting, Elsheikha, Hany M., Chen, Kai, Cong, Wei, Yang, Wen-Bin, Bai, Meng-Jie, Huang, Si-Yang and Zhu, Xing-Quan (2018) Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis. Journal of Infectious Diseases . ISSN 1537-6613 Toxoplasma gondii vaccination Ca2+-dependent protein kinase 2 attenuated vaccine protective immunity toxoplasmosis https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiy211/4969761 doi:10.1093/infdis/jiy211 doi:10.1093/infdis/jiy211
spellingShingle Toxoplasma gondii
vaccination
Ca2+-dependent protein kinase 2
attenuated vaccine
protective immunity
toxoplasmosis
Wang, Jin-Lei
Li, Ting-Ting
Elsheikha, Hany M.
Chen, Kai
Cong, Wei
Yang, Wen-Bin
Bai, Meng-Jie
Huang, Si-Yang
Zhu, Xing-Quan
Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis
title Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis
title_full Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis
title_fullStr Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis
title_full_unstemmed Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis
title_short Live-attenuated Pru: Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis
title_sort live-attenuated pru: δcdpk2 strain of toxoplasma gondii protects against acute, chronic and congenital toxoplasmosis
topic Toxoplasma gondii
vaccination
Ca2+-dependent protein kinase 2
attenuated vaccine
protective immunity
toxoplasmosis
url https://eprints.nottingham.ac.uk/51324/
https://eprints.nottingham.ac.uk/51324/
https://eprints.nottingham.ac.uk/51324/