Xiong Xiaolu, Qi Yong, Jiao Jun, Gong Wenping, Duan Changsong, Wen Bohai
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
PLoS One. 2014 Jan 30;9(1):e87206. doi: 10.1371/journal.pone.0087206. eCollection 2014.
Coxiella burnetii is a Gram-negative bacterium that causes Q fever in humans. In the present study, 131 candidate peptides were selected from the major immunodominant proteins (MIPs) of C. burnetii due to their high-affinity binding capacity for the MHC class II molecule H2 I-A(b) based on bioinformatic analyses. Twenty-two of the candidate peptides with distinct MIP epitopes were well recognized by the IFN-γ recall responses of CD4(+) T cells from mice immunized with parental proteins in an ELISPOT assay. In addition, 7 of the 22 peptides could efficiently induce CD4(+) T cells from mice immunized with C. burnetii to rapidly proliferate and significantly increase IFN-γ production. Significantly higher levels of IL-2, IL-12p70, IFN-γ, and TNF-α were also detected in serum from mice immunized with a pool of the 7 peptides. Immunization with the pool of 7 peptides, but not the individual peptides, conferred a significant protection against C. burnetii infection in mice, suggesting that these Th1 peptides could work together to efficiently activate CD4(+) T cells to produce the Th1-type immune response against C. burnetii infection. These observations could contribute to the rational design of molecular vaccines for Q fever.
伯纳特柯克斯体是一种革兰氏阴性细菌,可引起人类Q热。在本研究中,基于生物信息学分析,从伯纳特柯克斯体的主要免疫显性蛋白(MIPs)中筛选出131种候选肽,因其对MHC II类分子H2 I-A(b)具有高亲和力结合能力。在ELISPOT分析中,用亲本蛋白免疫的小鼠的CD4(+) T细胞的IFN-γ回忆反应很好地识别了22种具有不同MIP表位的候选肽。此外,这22种肽中的7种能够有效诱导用伯纳特柯克斯体免疫的小鼠的CD4(+) T细胞快速增殖,并显著增加IFN-γ的产生。在用7种肽的混合物免疫的小鼠血清中也检测到显著更高水平的IL-2、IL-12p70、IFN-γ和TNF-α。用7种肽的混合物而非单个肽免疫可使小鼠对伯纳特柯克斯体感染产生显著保护作用,这表明这些Th1肽可共同作用以有效激活CD4(+) T细胞,产生针对伯纳特柯克斯体感染的Th1型免疫反应。这些观察结果可能有助于Q热分子疫苗的合理设计。