Department of Child and Adolescent Medicine, University Hospitals of Geneva, Geneva, Switzerland.
Clin Microbiol Infect. 2012 Aug;18(8):756-62. doi: 10.1111/j.1469-0691.2011.03629.x. Epub 2011 Aug 18.
Pneumococcal surface proteins (PSPs) elicit antibody responses in infants and young children exposed to Streptococcus pneumoniae. These seroresponses could contribute to the aetiological diagnosis of pneumococcal disease, e.g. during the clinical development of novel PSP-based vaccines. In this study, we assessed the kinetics of antibody responses to three highly conserved and immunogenic PSPs (pneumococcal histidine triad D (PhtD), pneumococcal choline-binding protein A (PcpA), and serine proteinase precursor A (PrtA)) in 106 children (median age, 21.3 months; males, 58.5%) admitted for pneumococcal bacteraemia. Anti-PhtD, anti-PcpA and anti-PrtA antibodies were measured by ELISA, and compared in 61 pairs of acute (≤7 days) and convalescent (>14 days of admission) serum samples. Acute serum titres were similar to those observed in healthy children, and were unaffected by the acid dissociation of circulating immune complexes. Despite proven bacteraemia, seroresponses (≥2-fold increase in anti-PSP antibody concentrations) were only identified in 31 of 61 children (50.8%), directed against PrtA (n = 23, 37.7%), PcpA (n = 19, 31.1%), and PhtD (n = 16, 26.2%), or several PSPs (two PSPs, n = 13, 21.3%; three PSPs, n = 7, 11.5%). Certain seroresponses were very strong (maximal fold-increases: PhtD, 26; PcpA, 72; PrtA, 12). However, anti-PSP antibody concentrations failed to increase in the convalescent sera of 30 of 61 (49.2%) bacteraemic children, and even declined (≥2 fold) in 13 of 61 (21.3%), mostly infants aged <6 months (8/13, 61.5%), possibly through consumption of maternal antibodies. Thus, pneumococcal bacteraemia may fail to elicit antibody responses, and may even have an antibody-depleting effect in infants. This novel observation identifies an important limitation of serology-based studies for the identification of bacteraemic children.
肺炎球菌表面蛋白（PSP）在接触肺炎链球菌的婴儿和幼儿中引发抗体反应。这些血清反应可能有助于肺炎球菌疾病的病因诊断，例如在新型 PSP 为基础的疫苗的临床开发过程中。在这项研究中，我们评估了 106 名因肺炎球菌菌血症住院的儿童（中位年龄 21.3 个月；男性占 58.5%）对三种高度保守和免疫原性 PSP（肺炎球菌组氨酸三肽 D（PhtD）、肺炎球菌胆碱结合蛋白 A（PcpA）和丝氨酸蛋白酶前体 A（PrtA））的抗体反应动力学。通过 ELISA 测量抗 PhtD、抗 PcpA 和抗 PrtA 抗体，并在 61 对急性（≤7 天）和恢复期（入院后>14 天）血清样本中进行比较。急性血清滴度与健康儿童观察到的滴度相似，不受循环免疫复合物的酸解离影响。尽管已证实存在菌血症，但仅在 61 名儿童中的 31 名（50.8%）中识别出血清反应（抗 PSP 抗体浓度增加≥2 倍），针对 PrtA（n = 23，37.7%）、PcpA（n = 19，31.1%）和 PhtD（n = 16，26.2%）或几种 PSP（两种 PSP，n = 13，21.3%；三种 PSP，n = 7，11.5%）。某些血清反应非常强烈（最大倍数增加：PhtD，26；PcpA，72；PrtA，12）。然而，在 61 名菌血症儿童中的 30 名（49.2%）的恢复期血清中，抗 PSP 抗体浓度未能增加，甚至在 61 名中的 13 名（21.3%）中下降（≥2 倍），主要是年龄<6 个月的婴儿（13 分之 8，61.5%），可能是通过消耗了母体抗体。因此，肺炎球菌菌血症可能无法引发抗体反应，甚至可能对婴儿产生抗体耗竭作用。这一新的观察结果确定了基于血清学的研究识别菌血症儿童的一个重要局限性。
