Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom.
Am J Respir Crit Care Med. 2021 Mar 1;203(5):604-613. doi: 10.1164/rccm.202004-1483OC.
Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease. To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge. Sixty-four participants were inoculated with (serotype 6B; 80,000 cfu in each nostril). Colonization was determined by bacterial culture of nasal wash, and humoral immune responses were assessed by anticapsular and antiprotein IgG concentrations. Experimental colonization was established in 39% of participants (25/64) with no adverse events. Colonization occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonization. Colonization did not confer serotype-specific immune boosting, with a geometric mean titer (95% confidence interval) of 2.7 μg/ml (1.9-3.8) before the challenge versus 3.0 (1.9-4.7) 4 weeks after colonization ( = 0.53). Furthermore, pneumococcal challenge without colonization led to a drop in specific antibody concentrations from 2.8 μg/ml (2.0-3.9) to 2.2 μg/ml (1.6-3.0) after the challenge ( = 0.006). Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%). In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.
肺炎球菌定植是侵袭性疾病发病机制的关键，但在年轻成年人中也具有免疫原性，可防止再定植。尽管肺炎球菌疾病的发生率很高，但在老年人中很少检测到定植。本研究旨在建立 50-84 岁健康成年人的实验性人肺炎球菌定植，测量肺炎球菌挑战的免疫反应，并评估先前定植对同源株再挑战的保护作用。64 名参与者接种了（血清型 6B；每个鼻孔 80,000 个菌落形成单位）。通过鼻洗液的细菌培养来确定定植，通过抗荚膜和抗蛋白 IgG 浓度来评估体液免疫反应。实验性定植在 39%的参与者（25/64）中建立，无不良事件发生。在年龄 50-59 岁的参与者中，定植发生率为 47%（9/19），而在年龄≥70 岁的参与者中为 21%（3/14）。先前的肺炎球菌多糖疫苗接种不能预防定植。定植不会引起血清型特异性免疫增强，在挑战前几何平均滴度（95%置信区间）为 2.7μg/ml（1.9-3.8），而在定植后 4 周为 3.0μg/ml（1.9-4.7）（ = 0.53）。此外，没有定植的肺炎球菌挑战导致特异性抗体浓度从 2.8μg/ml（2.0-3.9）降至挑战后 2.2μg/ml（1.6-3.0）（ = 0.006）。成功定植后，抗蛋白抗体浓度增加。在中位时间 8.5 个月（四分位距，6.7-10.1）后用相同的菌株进行再挑战，导致 16 名参与者中的 5 名（31%）再次定植。在老年人中，实验性肺炎球菌定植是可行且安全的，但与之前研究中的年轻成年人相比，具有不同的免疫结果。
