灭活贝氏柯克斯体免疫小鼠抗登革病毒感染的实验研究

Efficacy of inactivated Coxiella burnetii against dengue virus infection in mice

目的研究灭活贝氏柯克斯体增强小鼠非特异性抗登革病毒感染的免疫效能。方法用灭活贝氏柯克斯体全细胞疫苗（WCV）免疫BALB／c小鼠，每只小鼠皮下注射50μgWCV，初次免疫后第5周及第7周分别腹腔注射20μg WCV加强免疫。1周后，用10^5 TCID50剂量的登革病毒2型经尾静脉注入感染小鼠，于感染后48、72h分别解剖小鼠，自血和脑组织提取RNA样本，用实时荧光定量聚合酶链反应（PCR）检测样本。结果用登革病毒特异的定量PCR检测感染小鼠血RNA样本，结果显示感染72h血样本中病毒含量显著低于48h样本，但免疫小鼠与未免疫小鼠之间无显著差异。检测脑组织RNA样本，未免疫小鼠和免疫小鼠的感染48h样本检出病毒均为少量；但未免疫小鼠感染96h样本检出病毒量明显增加，显著高于免疫小鼠。结论灭活贝氏柯克斯体可诱导机体产生非特异的免疫应答，具有一定增强小鼠抗登革病毒感染的能力，但具体机制有待进一步研究。

Objective To assess the efficacy of the Q fever vaccine against dengue virus infection. Methods The inactivated Coxiella burnerii （whole cell vaccine, WCV） was used to immunize BALB/c mice. For primary immunization, 50Vg WCV per monse was subcutaneously injected and 20μg WCV per mouse was intraperitoneally injected at Weeks 5 and 7 after primary immunization, respectively. One week after the last immunization, each mouse was challenged with 10s TCID50 of dengue virus via administration through the tail vein. The mice were sacrificed and blood and brain samples were collected 48 or 72 h after viral challenge. Samples were then examined by real-time quantitative PCR specific to dengue virus. Results In real-time quantitative PCR assay of blood samples, the amount of virus 72h postinfection was significantly lower than that observed at 48h and no significant difference was found between immunized mice and non-immunized mice. The amount of virus in brain samples from both non-immunized and immunized mice at 48h post infection was very low, however the amount of virus in brain samples from non-immunized mice rose sharply and was signifieanfly higher than that of immunized mice at 72h postinfection. Conclusion Non-specific immunoresponses against dengue virus infection may be induced by inactivated C. burnetii in mice.