肺炎链球菌疫苗候选抗原PspA异家族亚类间交叉反应评价

Analysis of serum cross-reactivity elicited by PspA fragments from different clades in patients with invasive pneumococcal disease

目的:观察肺炎链球菌DNA疫苗候选抗原肺炎链球菌表面蛋白A(PspA)在临床肺炎链球菌自然感染情况下家族分布及异家族亚类间抗原抗体交叉反应情况,探索肺炎链球菌PspA核酸疫苗的抗原组成形式。方法:采集我院42例临床侵入性肺炎链球菌感染菌株,及患者恢复期(第21±3天)的血清样本,同期确诊为非感染性疾病患者36例血清样本为对照组,细菌基因组特异性PCR及测序比对鉴定PspA家族分布,酶联免疫吸附法(ELISA)检测患者血清PspA抗体与PspA蛋白6种亚类抗原的交叉反应情况。结果:42株肺炎链球菌中以PspA家族Fam1-Clade2(31.0%)和Fam2-Clade3(47.6%)的菌株为优势分布,所有侵入性肺炎链球菌感染患者血清中针对PspA-Fam1特异性抗体水平高于针对PspA-Fam2的特异性抗体水平,血清PspA抗体与PspA蛋白6种亚类抗原的交叉反应发现异家族各亚类间交叉反应弱,但同家族亚类间显著交叉反应以Fam1-Clade1和Fam2-Clade3为优势。结论:肺炎链球菌PspA核酸疫苗靶抗原的组成时应同时包括产生高保护性抗体效价和强交叉反应的Fam1及Fam2的优势Clade亚类成分才能有效针对广泛的临床致病肺炎链球菌菌株感染的保护。

Objective： To investigate antibody cross-reactivity to six clades of Streptococcus pneumoniae surface proteins A （PspA） in patients with invasive pneumococcal disease （IPD）, and choose the prevalent formats of clades of PspA for Streptococcus pneumoniae DNA vaccine. Methods： 42 Streptococcus pneumoniae strains were collected from patients hospitalized with IPD, and convalescent the serum samples （（21±3） days later）were obtained from the 42 patients. We characterized serum antibody cross-reactivity to 6 clades of PspA in 36 adults hospitalized with IPD by ELISA, and 36 patients hospitalized for non infectious conditions as control group. All pneumococcal isolates were typed for the PspA family and clades. And antibody levels to PspA-Faml were higher than antibody levels to PspA-Fam2. Results： The strains containing Faml-Clade2（31.0%）and Fam2-Clade3（47.6%）were the most prevalent in 42 pneumococcal isolates. Conclusion： our results reinforce the notion that in order to produce a PspA based vaccine it will be necessary to use prevalent clades to obtain high coverage.