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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 ME49\u0394\n                    <jats:italic>cdpk3<\/jats:italic>\n                    as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49\u0394\n                    <jats:italic>cdpk3<\/jats:italic>\n                    vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-\u03b3, IL-12, and TNF-\u03b1, and increased the percentage of CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2009and CD8\n                    <jats:sup>+<\/jats:sup>\n                    \u2009T-lymphocytes. The high level of\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    -specific IgG was maintained, with mixed IgG1\/IgG2a levels. Mice vaccinated with ME49\u0394\n                    <jats:italic>cdpk3<\/jats:italic>\n                    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 ME49\u0394\n                    <jats:italic>cdpk3<\/jats:italic>\n                    inoculation induced effective cellular and humoral immune responses against acute and chronic\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.\n                  <\/jats:p>","DOI":"10.1038\/s41541-022-00518-5","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T23:24:48Z","timestamp":1660951488000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Live-attenuated ME49\u0394cdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8138-2247","authenticated-orcid":false,"given":"Minmin","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-6544","authenticated-orcid":false,"given":"Shutong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-5402","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6800-1075","authenticated-orcid":false,"given":"Deng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-4815","authenticated-orcid":false,"given":"Ran","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-3405","authenticated-orcid":false,"given":"Haijian","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-970X","authenticated-orcid":false,"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7629-3602","authenticated-orcid":false,"given":"Nan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-6636","authenticated-orcid":false,"given":"Cudjoe","family":"Obed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2775-8738","authenticated-orcid":false,"given":"Meng","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4755-3687","authenticated-orcid":false,"given":"Jilong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-5645","authenticated-orcid":false,"given":"Lijian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,20]]},"reference":[{"key":"518_CR1","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.ijpara.2009.01.005","volume":"39","author":"JP Dubey","year":"2009","unstructured":"Dubey, J. 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