Clinical Pharmacology and Drug Metabolism/Pharmacokinetics, MedImmune, Gaithersburg, Maryland, USA.
Clinical Pharmacology and Drug Metabolism/Pharmacokinetics, MedImmune, Mountain View, California, USA.
Infect Immun. 2018 Feb 20;86(3). doi: 10.1128/IAI.00671-17. Print 2018 Mar.
causes an array of serious infections resulting in high morbidity and mortality worldwide. This study evaluated naturally occurring serum anti-alpha-toxin (anti-AT) antibody levels in human subjects from various age groups, individuals with dialysis and surgical-site infections, and -colonized versus noncolonized subjects. Anti-AT immunoglobulin G (IgG) and neutralizing antibody (NAb) levels in infants (aged ≤1 year) were significantly lower than those in other populations. In comparison to adolescent, adult, and elderly populations, young children (aged 2 to 10 years) had equivalent anti-AT IgG levels but significantly lower anti-AT NAb levels. Therefore, the development of anti-AT NAbs appears to occur later than that of AT-specific IgG, suggesting a maturation of the immune response to AT. Anti-AT IgG levels were slightly higher in -colonized subjects than in noncolonized subjects. The methicillin susceptibility status of colonizing isolates had no effect on anti-AT antibody levels in -colonized subjects. The highest anti-AT IgG and NAb levels were observed in dialysis patients with acute infection. Anti-AT IgG and NAb levels were well correlated in subjects aged >10 years, regardless of colonization or infection status. These data demonstrate that AT elicits a robust IgG humoral response in infants and young children that becomes stable prior to adolescence, matures into higher levels of NAbs in healthy adolescents, and becomes elevated during infection. These findings may assist in identifying subjects and patient populations that could benefit from vaccination or immunoprophylaxis with anti-AT monoclonal antibodies.
导致了一系列严重的感染,在全球范围内导致了高发病率和死亡率。本研究评估了来自不同年龄组的人类受试者、透析和手术部位感染患者以及定植与非定植受试者中天然存在的血清抗α-毒素(抗-AT)抗体水平。婴儿(≤1 岁)的抗-AT 免疫球蛋白 G(IgG)和中和抗体(NAb)水平明显低于其他人群。与青少年、成年和老年人群相比,幼儿(2 至 10 岁)具有等效的抗-AT IgG 水平,但抗-AT NAb 水平明显较低。因此,抗-AT NAb 的产生似乎晚于 AT 特异性 IgG 的产生,这表明对 AT 的免疫反应正在成熟。定植受试者的抗-AT IgG 水平略高于非定植受试者。定植分离株的甲氧西林敏感性状态对定植受试者的抗-AT 抗体水平没有影响。在急性感染的透析患者中观察到最高的抗-AT IgG 和 NAb 水平。在>10 岁的受试者中,无论是否存在定植或感染状态,抗-AT IgG 和 NAb 水平均呈良好相关性。这些数据表明,AT 在婴儿和幼儿中引起强烈的 IgG 体液反应,在青春期前变得稳定,在健康青少年中成熟为更高水平的 NAb,并在感染期间升高。这些发现可能有助于确定可能受益于抗-AT 单克隆抗体疫苗接种或免疫预防的受试者和患者群体。