肺炎链球菌毒力蛋白在侵入性感染中的免疫原性评价

Study of immunogenicity of PspA,Ply and PsaA in adults with invasive pneumococcal disease

目的观察肺炎链球菌表面蛋白A(PspA)、肺炎链球菌表面黏附素A(PsaA)及肺炎链球菌溶菌素(Ply)激发自然途径感染肺炎链球菌机体保护性体液免疫应答的情况,评价这三种毒力蛋白作为治疗性肺炎链球菌疫苗候选抗原的免疫原性。方法采集侵入性肺炎链球菌感染患者(实验组)及同期确诊为侵入性其它细菌感染患者(对照第一组)和同期确诊为非感染性疾病患者(对照第二组)各36例急性期(第0+3天)及恢复期(第21±3天)血清样本,酶联免疫吸附法(ELISA)检测患者血清中肺炎链球菌3种毒力蛋白抗原特异性抗体IgG水平变化。结果实验组与两组对照组间第(0+3)天血清的3种肺炎链球菌毒力蛋白特异性抗体水平无显著性差异(P>0.05)。第一组对照组恢复期较急性期血清中3种毒力蛋白特异性抗体水平无显著变化(P>0.05),而实验组恢复期血清3种肺炎链球菌毒力蛋白特异性抗体水平明显高于急性期血清抗体水平8～30倍(P<0.01),其中PspA和Ply蛋白抗原特异性抗体水平升高更明显,血清中针对PspA家族1(PspA-Faml)特异性抗体水平高于针对PspA家族2(PspA-Fam2)的特异性抗体水平(P<0.01)。结论 PsaA,PspA及Ply均为具有免疫原性的肺炎链球菌菌体成分,其中PspA和Ply特异性抗体在人体自然途径的肺炎链球菌感染中发挥更重要的保护性作用,可作为新一代治疗性肺炎链球菌疫苗理想的侯选抗原。

To investigate antibody responses to three Streptococcus pneumoniae surface proteins, PspA, Ply, and PsaA, in adults with invasive pneumococcal disease （IPD）, in consideration of taking the three proteins as candidate antigens of Streptococcus pneumoniae vaccine. We characterized antibody responses to PspA, Ply and PsaA, in 36 aduhs hospitalized with IPD, and in two groups of age-matched controls （group 1：36 patients with invasive disease due to other microorganisms and group 2：36 patients hospitalized for non infectious conditions）. All pneumococcal isolates were typed for the PspA family. Acute serum samples [（0＋3） days] and convalescent samples [（21 ±3） days later] were obtained from IPD subjects and control group 1, while single serum samples were obtained from control group2. Antibody levels to PspA-Faml, PspA-Fam2, Ply and PsaA were measured by ELISA. All antibody concentrations in acute samples from IPD subjects were similar to those from patients of group 1 and group 2 （P〉 0.05）. The antibody levels to three antigens were similar in acute and convalescent sera from group 1 （P〉 0.05）, in contrast, the geometric mean antibody concentrations to the three proteins in the convalescent sera of IPD patients were 8 and 30 times higher than those in the corresponding acute sera （P 〈 0.01）, especially, the raise of anti-PspA and anti-Ply levels in convalescent sera of IPD patients were more significant than that of anti-PsaA level. Antibody levels to PspA-Faml were higher than antibody levels to PspA-Fam2 （P 〈 0.01）. The results above showed that PsaA, PspA, and Ply all have immunogenicity as the components of Streptococcus pneumonia. And antibodies to PspA and Ply have significant protective effects against IPD, which suggest the two proteins could be considered as important candidate antigens for novel vaccine design for the treatment.