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This study aimed to provide an optimized animal model for future studies of\n                      <jats:italic>Cryptosporidium<\/jats:italic>\n                      vaccine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Three mouse strains (ICR, BALB\/c and KM) with or without immunosuppression were compared after challenge with\n                      <jats:italic>Cryptosporidium tyzzeri<\/jats:italic>\n                      (\n                      <jats:italic>C\u00a0tyzzeri<\/jats:italic>\n                      ). The results indicated that ICR mice shed a greater number of faecal oocysts (20\u00a0346\u00a0\u00b1\u00a0203 oocysts\/g) compared with BALB\/c (2077\u00a0\u00b1\u00a0142 oocysts\/g) and KM mice (3207\u00a0\u00b1\u00a0431 oocysts\/g) after experimental infection with\n                      <jats:italic>C\u00a0tyzzeri<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). However, ICR mouse model is uniquely effective for\n                      <jats:italic>C\u00a0tyzzeri<\/jats:italic>\n                      , not for other\n                      <jats:italic>Cryptosporidium<\/jats:italic>\n                      spp. such as\n                      <jats:italic>C\u00a0parvum<\/jats:italic>\n                      . ICR mice were then used to determine the immunoreactions and immunoprotection of P23\u2010DNA vaccine (pVAX1\u2010P23) to\n                      <jats:italic>C\u00a0tyzzeri<\/jats:italic>\n                      experimental infection. The results showed that a significant increase in anti\u2010P23 antibody levels was induced by the pVAX1\u2010P23 vaccine. Compared to pVAX1, TB and blank control mice, pVAX1\u2010P23 immunized mice produced specific spleen cell proliferation as well as enhanced IL\u20105, IL\u201012p70 and IFN\u2010\u03b3 production in sera. After challenge with 5\u00a0\u00d7\u00a010\n                      <jats:sup>6<\/jats:sup>\n                      <jats:italic>C\u00a0tyzzeri<\/jats:italic>\n                      oocysts, the oocyst shedding of the pVAX1\u2010P23 immunized group was reduced by 69.94% comparing to the infection control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These results provide an optimized animal model for the study of prophylactic vaccines and this model might be applied to other candidates against\n                      <jats:italic>Cryptosporidium<\/jats:italic>\n                      , not only for pVAX1\u2010P23.\n                    <\/jats:p>\n                  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