Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan.
Taipei Medical University, Taipei, Taiwan.
Respir Res. 2018 Sep 25;19(1):187. doi: 10.1186/s12931-018-0895-8.
Streptococcus pneumoniae is a respiratory pathogen causing severe lung infection that may lead to complications such as bacteremia. Current polysaccharide vaccines have limited serotype coverage and therefore cannot provide maximal and long-term protection. Global efforts are being made to develop a conserved protein vaccine candidate. PrtA, a pneumococcal surface protein, was identified by screening a pneumococcal genomic expression library using convalescent patient serum. The prtA gene is prevalent and conserved among S. pneumoniae strains. Its protective efficacy, however, has not been described. Mucosal immunization could sensitize both local and systemic immunity, which would be an ideal scenario for preventing S. pneumoniae infection.
We immunized BALB/c mice intranasally with a combination of a PrtA fragment (amino acids 144-1041) and Th17 potentiated adjuvant, curdlan. We then measured the T-cell and antibody responses. The protective efficacy conferred to the immunized mice was further evaluated using a murine model of acute pneumococcal pneumonia and pneumococcal bacteremia.
There was a profound antigen-specific IL-17A and IFN-γ response in PrtA-immunized mice compared with that of adjuvant control group. Even though PrtA-specific IgG and IgA titer in sera was elevated in immunized mice, only a moderate IgA response was observed in the bronchoalveolar lavage fluid. The PrtA-immunized antisera facilitated the activated murine macrophage, RAW264.7, to opsonophagocytose S. pneumoniae D39 strain; however, PrtA-specific immunoglobulins bound to pneumococcal surfaces with a limited potency. Finally, PrtA-induced immune reactions failed to protect mice against S. pneumoniae-induced acute pneumonia and bacterial propagation through the blood.
Immunization with recombinant PrtA combined with curdlan produced antigen-specific antibodies and elicited IL-17A response. However, it failed to protect the mice against S. pneumoniae-induced infection.
肺炎链球菌是一种呼吸道病原体，可导致严重肺部感染，进而引发菌血症等并发症。目前的多糖疫苗针对的血清型有限，因此无法提供最大和长期的保护。全球正在努力开发一种保守的蛋白质疫苗候选物。通过使用恢复期患者血清筛选肺炎链球菌基因组表达文库，发现了肺炎球菌表面蛋白 PrtA。该基因在肺炎链球菌菌株中普遍存在且保守。然而，其保护效果尚未得到描述。黏膜免疫可以增强局部和全身免疫，这将是预防肺炎链球菌感染的理想情况。
我们通过鼻腔内免疫 BALB/c 小鼠，用肺炎球菌表面蛋白 PrtA 片段（氨基酸 144-1041）和 Th17 增强佐剂几丁质组合，然后测量 T 细胞和抗体反应。通过急性肺炎球菌肺炎和肺炎球菌菌血症的小鼠模型进一步评估免疫接种小鼠的保护效力。
与佐剂对照组相比，PrtA 免疫小鼠表现出深刻的抗原特异性白细胞介素 17A 和干扰素-γ反应。尽管免疫小鼠血清中的 PrtA 特异性 IgG 和 IgA 滴度升高，但在支气管肺泡灌洗液中仅观察到适度的 IgA 反应。PrtA 免疫血清促进了激活的鼠巨噬细胞 RAW264.7 吞噬肺炎球菌 D39 株；然而，PrtA 特异性免疫球蛋白与肺炎球菌表面的结合能力有限。最后，PrtA 诱导的免疫反应未能保护小鼠免受肺炎球菌引起的急性肺炎和细菌通过血液传播。
用重组 PrtA 与几丁质联合免疫可产生针对抗原的抗体并引发白细胞介素 17A 反应。然而，它未能保护小鼠免受肺炎球菌引起的感染。
