T-B cell epitope peptides induce protective immunity against Mycoplasma pneumoniae respiratory tract infection in BALB/c mice
T-B cell epitope peptides induce protective immunity against Mycoplasma pneumoniae respiratory tract infection in BALB/c mice
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T-B细胞表位肽诱导BALB/c小鼠抵抗肺炎支原体呼吸道感染的保护性免疫
DOI：
10.1016/j.imbio.2021.152077
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发表时间：
2021-04-05
期刊：
影响因子：
2.8
通讯作者：
You, Xiaoxing
中科院分区：
文献类型：
--
作者：
Chen, Yiwen;Wu, Yueyue;You, Xiaoxing
肺炎支原体是人类社区获得性肺炎最常见的病原体。由于其对抗生素的高耐药率，接种疫苗已成为控制肺炎支原体传播的最佳方法。重组P1(P1C)蛋白的羧基末端是一种免疫优势抗原，但存在稳定性差、纯度低等缺点。在本研究中，根据生物信息学分析预测了P1C蛋白的T-B表位，并对其在多肽疫苗接种中的效果进行了评估。给BALB/c小鼠皮下接种T-B表位多肽4次，然后通过呼吸道感染肺炎支原体。结果表明，P1C蛋白的T-B表位多肽(P1C(103-117)、P1C(155-169)、P1C(224-238)和P1C(244-258))可诱导较强的抗原特异性血清抗体应答和细胞免疫应答，并产生较高水平的血清抗体、IgA抗体和Th1偏向的细胞因子(干扰素-γ和IL-2)。T-B表位多肽免疫可显著降低肺炎支原体感染负荷和炎症程度。此外，肺组织匀浆上清液中的干扰素-γ和肿瘤坏死因子-α水平明显低于假手术组。总体而言，我们的研究结果表明T-B表位(P1C(103-117)、P1C(155-169)、P1C(224-238)和P1C(244-258))在P1C蛋白中发挥重要作用，可用于诱导强大的体液和细胞免疫反应，从而对肺炎支原体肺部感染提供显著保护，这为设计潜在的多表位疫苗以预防宿主肺炎支原体感染提供了新的见解。
Mycoplasma pneumoniae is the most common pathogen of community-acquired pneumonia in humans. Due to its high rates of antibiotic resistance, vaccination has become the best method to control the dissemination of M. pneumoniae. The recombinant carboxyl terminus of the P1 (P1C) protein is an immunodominant antigen, but it has negative effects such as poor stability and lower purity. In the current study, T-B epitopes of the P1C protein were predicted according to bioinformatics analysis and assessed for efficacy in peptide vaccination. BALB/c mice were subcutaneously inoculated with the T-B epitope peptides four times and then infected with M. pneumoniae through the respiratory tract. The results showed that the T-B epitope peptides of the P1C protein (P1C(103-117), P1C(155-169,) P1C(224-238) and P1C(244-258)) induced strong antigen-specific serum antibody responses and cellular immune responses with high levels of serum IgG, IgA antibodies and Th1-biased (IFN-gamma and IL-2) cytokines. Immunization with T-B epitope peptides significantly reduced the M. pneumoniae burden and the degree of inflammation in the challenged mice. Furthermore, the levels of IFN-gamma and TNF-alpha in the supernatants of lung homogenates were observably reduced compared to those in the PBS group. Overall, our findings demonstrate that T-B epitopes (P1C(103-117), P1C(155-169), P1C(224-238) and P1C(244-258)) play significant roles in the P1C protein and can be used to induce powerful humoral and cellular immune responses to provide significant protection against M. pneumoniae pulmonary infection, which provides new insight into the design of potential multiepitope vaccines to prevent host infection by M. pneumoniae.