Development of an immunocompetent mouse model susceptible to Cryptosporidium tyzzeri infection.

AIMS Immunocompromised mice are extensively used in the screening of vaccines and drugs for Cryptosporidium, but this study model does not reflect the real status of infection in immunocompetent animals. This study aimed to provide an optimized animal model for future studies of Cryptosporidium vaccine. METHODS AND RESULTS Three mouse strains (ICR, BALB/c, and KM) with or without immunosuppression were compared after challenge with Cryptosporidium tyzzeri (C. tyzzeri). The results indicated that ICR mice shed a greater number of fecal oocysts (20,346 ± 203 oocysts/g) compared with BALB/c (2077 ± 142 oocysts/g) and KM mice (3,207 ± 431 oocysts/g) after experimental infection with C. tyzzeri (P<0.001). However, ICR mouse model is uniquely effective for C. tyzzeri, not for other Cryptosporidium spp. such as C. parvum. ICR mice were then used to determine the immunoreactions and immunoprotection of P23-DNA vaccine (pVAX1-P23) to C. tyzzeri experimental infection. The results showed that a significant increase in anti-P23 antibody levels was induced by the pVAX1-P23 vaccine. Compared to pVAX1, TB and blank control mice, pVAX1-P23 immunized mice produced specific spleen cell proliferation as well as enhanced IL-5, IL-12p70 and IFN-γproduction in sera. After challenge with 5×106 C. tyzzeri oocysts, the oocyst shedding of the pVAX1-P23 immunized group was reduced by 69.94% comparing to the infection control. CONCLUSION These results provide an optimized animal model for the study of prophylactic vaccines and this model might be applied to other candidates against Cryptosporidium, not only for pVAX1-P23.\.