Chlamydial protease-like activity factor mediated protection against C. trachomatis in guinea pigs.
Chlamydial protease-like activity factor mediated protection against C. trachomatis in guinea pigs.
复制标题
DOI：
10.1038/icb.2016.122
复制
发表时间：
2017-05
影响因子：
4
通讯作者：
Arulanandam BP
中科院分区：
文献类型：
--
作者：
Wali S;Gupta R;Yu JJ;Lanka GKK;Chambers JP;Guentzel MN;Zhong G;Murthy AK;Arulanandam BP
我们已经通过小鼠模型全面证明，重组衣原体蛋白酶样活性因子（rCPAF）鼻内免疫可显著减少阴道内生殖器衣原体攻击后的细菌负担、生殖道病理和生育能力。在本报告中，我们评估了rCPAF免疫在豚鼠（生殖器衣原体感染的第二种动物模型）中的保护效果。使用与小鼠模型相似的疫苗接种策略，我们用rcppaf加CpG脱氧核苷酸（CpG；作为佐剂）鼻内免疫雌性豚鼠，并阴道内感染沙眼原体血清型D （CT-D）。与CpG单独处理和攻毒的动物相比，rCPAF/CpG免疫可显著减少阴道CT-D脱落，并在第24天诱导感染消退。在最后一次免疫后2周，免疫诱导了强效的抗rcpaf血清IgG，并在攻击后4周维持在高水平。在rCPAF/CpG免疫的脾细胞中，抗原特异性IFN-γ基因表达上调。重要的是，与cpg免疫的动物相比，观察到rCPAF/ cpg免疫的豚鼠生殖器组织炎症显著减少。综上所述，本研究为rCPAF作为第二种生殖器衣原体感染动物模型的候选疫苗的保护作用提供了证据。
We have comprehensively demonstrated using the mouse model that intranasal immunization with recombinant chlamydial protease-like activity factor (rCPAF) leads to a significant reduction in bacterial burden, genital tract pathology and preserves fertility following intravaginal genital chlamydial challenge. In the present report, we evaluated the protective efficacy of rCPAF immunization in guinea pigs, a second animal model for genital chlamydial infection. Using a vaccination strategy similar to the mouse model, we intranasally immunized female guinea pigs with rCPAF plus CpG deoxynucleotides (CpG; as an adjuvant), and challenged intravaginally with C. trachomatis serovar D (CT-D). Immunization with rCPAF/CpG significantly reduced vaginal CT-D shedding and induced resolution of infection by day 24, compared to day 33 in CpG alone treated and challenged animals. Immunization induced robust anti-rCPAF serum IgG 2 weeks following the last immunization, and was sustained at a high level 4 weeks post challenge. Upregulation of antigen specific IFN-γ gene expression was observed in rCPAF/CpG vaccinated splenocytes. Importantly, a significant reduction in inflammation in the genital tissue in rCPAF/CpG-immunized guinea pigs compared to CpG-immunized animals was observed. Taken together, this study provides evidence of the protective efficacy of rCPAF as a vaccine candidate in a second animal model of genital chlamydial infection.