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To date, an ideal vaccine against toxoplasmosis has not yet been developed. Our previous study demonstrated that deletion of the\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      p\n                      <jats:italic toggle=\"yes\">CaBP<\/jats:italic>\n                      gene, which encodes a calcium-binding EF-hand protein, impaired calcium flux, invasion, and egress, thereby reducing\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      virulence. However, the mechanisms underlying this loss of virulence and the potential of RH\u0394\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      p\n                      <jats:italic toggle=\"yes\">CaBP<\/jats:italic>\n                      as a live attenuated vaccine remain unclear. Here, we showed that\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      p\n                      <jats:italic toggle=\"yes\">CaBP<\/jats:italic>\n                      deletion significantly downregulated the expression of proteins associated with invasion, egress, and pyrimidine metabolism.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      evaluations revealed that co-administration of RH\u0394\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      pCaBP and sulfadiazine showed limited pathological adverse effects in mice\u2014all mice survived immunization with 100 tachyzoites without obvious organ injury, and conferred protection against lethal wild-type RH strain challenge (\u22641,000 tachyzoites). Flowcytometry assays demonstrated that RH\u0394\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      pCaBP strain immunization increased IFN-\u03b3 production in circulating CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and the frequencies of splenic CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      effector memory T cells, memory B cells, and activated B cells. In conclusion,\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      p\n                      <jats:italic toggle=\"yes\">CaBP<\/jats:italic>\n                      plays an important role in regulating the virulence of\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      by modulating the expression of proteins related to pyrimidine metabolism, invasion, and egress. Co-immunization with 100 RH\u0394\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      pCaBP tachyzoites and sulfadiazine shows favorable safety profiles and protective efficacy in mice, triggers observable immune memory, and may serve as a promising candidate for an attenuated live vaccine against toxoplasmosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Toxoplasmosis, caused by\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      , poses substantial public health and economic burdens worldwide. Although medicinal plants are traditionally the most promising source for the treatment of toxoplasmosis, no effective therapeutic regimen has been developed to date. Thus, the development of safe, effective, and long-lasting vaccines has become key for the prevention and control of toxoplasmosis. This study demonstrated that the deletion of\n                      <jats:italic toggle=\"yes\">TgpCaBP<\/jats:italic>\n                      , a gene encoding an EF-hand calcium-binding protein, profoundly attenuated the virulence of the virulent RH strain by disrupting key pathogenic processes. More importantly, the RH\u0394\n                      <jats:italic toggle=\"yes\">TgpCaBP<\/jats:italic>\n                      strain, administered in combination with sulfadiazine, emerged as a promising live attenuated vaccine candidate. It exhibited favorable safety profiles in mice and elicited an immunomodulatory trend. Although further optimization is warranted, this study establishes a foundational framework for developing live attenuated vaccines against toxoplasmosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01827-26","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:03:43Z","timestamp":1789650223000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Role of\n                    <i>Toxoplasma gondii<\/i>\n                    calcium-binding protein (\n                    <i>Tg<\/i>\n                    pCaBP) and its implications for the development of attenuated live vaccines"],"prefix":"10.1128","volume":"14","author":[{"given":"Yiwei","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n7x9n08","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Livestock Infectious Diseases, 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