Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
Parasite Immunol. 2021 Jan;43(1):e12800. doi: 10.1111/pim.12800. Epub 2020 Nov 1.
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.
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 faecal oocysts (20 346 ± 203 oocysts/g) compared with BALB/c (2077 ± 142 oocysts/g) and KM mice (3207 ± 431 oocysts/g) after experimental infection with C tyzzeri (P < .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-γ production in sera. After challenge with 5 × 10 C tyzzeri oocysts, the oocyst shedding of the pVAX1-P23 immunized group was reduced by 69.94% comparing to the infection control.
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.
免疫功能低下的小鼠被广泛用于筛选隐孢子虫疫苗和药物，但这种研究模型并不能反映免疫功能正常动物的真实感染状态。本研究旨在为隐孢子虫疫苗的未来研究提供一种优化的动物模型。
比较了三种有或无免疫抑制的小鼠品系（ICR、BALB/c 和 KM）在感染伯氏隐孢子虫（C tyzzeri）后的情况。结果表明，ICR 小鼠在感染 C tyzzeri 后排出的粪便卵囊数量（20 346 ± 203 个/克）明显多于 BALB/c（2077 ± 142 个/克）和 KM 小鼠（3207 ± 431 个/克）（P <.001）。然而，ICR 小鼠模型仅对 C tyzzeri 有效，而对其他隐孢子虫种如 C parvum 无效。然后，我们使用 ICR 小鼠来确定 P23-DNA 疫苗（pVAX1-P23）对 C tyzzeri 实验感染的免疫反应和免疫保护作用。结果表明，pVAX1-P23 疫苗显著诱导了抗 P23 抗体水平的升高。与 pVAX1、TB 和空白对照组相比，pVAX1-P23 免疫组小鼠产生了特异性的脾细胞增殖，并增强了血清中 IL-5、IL-12p70 和 IFN-γ的产生。在感染 5×10 个 C tyzzeri 卵囊后，与感染对照组相比，pVAX1-P23 免疫组的卵囊排出量减少了 69.94%。
这些结果为预防性疫苗的研究提供了一种优化的动物模型，该模型可能适用于其他针对隐孢子虫的候选疫苗，而不仅仅是 pVAX1-P23。
