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

Wang, Jin-Lei; Liang, Qin-Li; Li, Ting-Ting; He, Jun-Jun; Bai, Meng-Jie; Cao, Xue-Zhen; Elsheikha, Hany M.; Zhu, Xing-Quan

Abstract

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.

Citation

Wang, J.-L., Liang, Q.-L., Li, T.-T., He, J.-J., Bai, M.-J., Cao, X.-Z., Elsheikha, H. M., & Zhu, X.-Q. (2020). Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice. Journal of Immunology, 204(6), 1562-1570. https://doi.org/10.4049/jimmunol.1900410

• Journal Article Type: Article
• Acceptance Date: Jan 1, 2020
• Online Publication Date: Jan 29, 2020
• Publication Date: Mar 15, 2020
• Deposit Date: Feb 1, 2020
• Journal: Journal of Immunology
• Print ISSN: 0022-1767
• Electronic ISSN: 1550-6606
• Publisher: American Association of Immunologists
• Peer Reviewed: Peer Reviewed
• Volume: 204
• Issue: 6
• Pages: 1562-1570
• DOI: https://doi.org/10.4049/jimmunol.1900410
• Keywords: Immunology
• Public URL: https://nottingham-repository.worktribe.com/output/3842152
• Publisher URL: https://www.jimmunol.org/content/early/2020/01/28/jimmunol.1900410