Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
Abstract Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-08-01
|
| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-022-00518-5 |
| _version_ | 1797642432343441408 |
|---|---|
| author | Minmin Wu Shutong Liu Ying Chen Deng Liu Ran An Haijian Cai Jie Wang Nan Zhou Cudjoe Obed Meng Han Jilong Shen Lijian Chen Jian Du |
| author_facet | Minmin Wu Shutong Liu Ying Chen Deng Liu Ran An Haijian Cai Jie Wang Nan Zhou Cudjoe Obed Meng Han Jilong Shen Lijian Chen Jian Du |
| author_sort | Minmin Wu |
| collection | DOAJ |
| description | Abstract Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4+ and CD8+ T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis. |
| first_indexed | 2024-03-11T14:01:10Z |
| format | Article |
| id | doaj.art-57df80eb3d0f449f9872b461e46a7b45 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-11T14:01:10Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-57df80eb3d0f449f9872b461e46a7b452023-11-02T04:39:22ZengNature Portfolionpj Vaccines2059-01052022-08-017111010.1038/s41541-022-00518-5Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosisMinmin Wu0Shutong Liu1Ying Chen2Deng Liu3Ran An4Haijian Cai5Jie Wang6Nan Zhou7Cudjoe Obed8Meng Han9Jilong Shen10Lijian Chen11Jian Du12Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityThe Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityThe Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityThe Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityThe Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityAbstract Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4+ and CD8+ T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.https://doi.org/10.1038/s41541-022-00518-5 |
| spellingShingle | Minmin Wu Shutong Liu Ying Chen Deng Liu Ran An Haijian Cai Jie Wang Nan Zhou Cudjoe Obed Meng Han Jilong Shen Lijian Chen Jian Du Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis npj Vaccines |
| title | Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis |
| title_full | Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis |
| title_fullStr | Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis |
| title_full_unstemmed | Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis |
| title_short | Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis |
| title_sort | live attenuated me49δcdpk3 strain of toxoplasma gondii protects against acute and chronic toxoplasmosis |
| url | https://doi.org/10.1038/s41541-022-00518-5 |
| work_keys_str_mv | AT minminwu liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT shutongliu liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT yingchen liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT dengliu liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT ranan liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT haijiancai liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT jiewang liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT nanzhou liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT cudjoeobed liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT menghan liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT jilongshen liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT lijianchen liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis AT jiandu liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis |