用于检测人尿液中 11 种额外肺炎链球菌血清型特异性多糖的免疫诊断检测方法的鉴定和临床验证。
Qualification and Clinical Validation of an Immunodiagnostic Assay for Detecting 11 Additional Streptococcus pneumoniae Serotype-specific Polysaccharides in Human Urine.
机构信息
Vaccine Research and Development,Pfizer Research, Pearl River, New York, USA.
Early Clinical Development, Pfizer Research, Pearl River, New York, USA.
出版信息
Clin Infect Dis. 2020 Dec 3;71(9):e430-e438. doi: 10.1093/cid/ciaa158.
BACKGROUND
Identifying Streptococcus pneumoniae serotypes by urinary antigen detection (UAD) assay is the most sensitive way to evaluate the epidemiology of nonbacteremic community-acquired pneumonia (CAP). We first described a UAD assay to detect the S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, covered by the licensed 13-valent S. pneumoniae conjugate vaccine. To assess the substantial remaining pneumococcal disease burden after introduction of several pneumococcal vaccines, a UAD-2 assay was developed to detect 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F) in individuals with radiographically confirmed CAP.
METHODS
The specificity of the UAD-2 assay was achieved by capturing pneumococcal polysaccharides with serotype-specific monoclonal antibodies, using Luminex technology. Assay qualification was used to assess accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by nonparametric statistical evaluation of urine samples from individuals without pneumococcal disease. The sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation, using urine samples obtained from a large study that measured the proportion of radiographically confirmed CAP caused by S. pneumoniae serotypes in hospitalized US adults.
RESULTS
The UAD-2 assay was shown to be specific and reproducible. Clinical validation demonstrated assay sensitivity and specificity of 92.2% and 95.9% against a reference standard of bacteremic pneumonia. In addition, the UAD-2 assay identified a S. pneumoniae serotype in 3.72% of nonbacteremic CAP cases obtained from hospitalized US adults. When combined with bacteremic CAP cases, the proportion of pneumonias with a UAD-2 serotype was 4.33%.
CONCLUSIONS
The qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic S. pneumoniae CAP and for assessing the efficacy of future pneumococcal conjugate vaccines that are under development.
背景
通过尿抗原检测（UAD）试验鉴定肺炎链球菌血清型是评估非菌血症性社区获得性肺炎（CAP）流行病学的最敏感方法。我们首次描述了一种 UAD 试验，用于检测经许可的 13 价肺炎链球菌结合疫苗涵盖的血清型 1、3、4、5、6A、6B、7F、9V、14、18C、19A、19F 和 23F。为了评估在引入几种肺炎球菌疫苗后仍存在大量肺炎球菌疾病负担，开发了 UAD-2 试验来检测放射学确诊 CAP 患者中的 11 种额外血清型（2、8、9N、10A、11A、12F、15B、17F、20、22F 和 33F）。
方法
通过使用 Luminex 技术用针对特定血清型的单克隆抗体捕获肺炎链球菌多糖，实现了 UAD-2 试验的特异性。试验资格用于评估准确性、精密度和样品线性度。血清型阳性基于非参数统计方法对无肺炎球菌病个体的尿液样本进行评估确定的截定点。在一项临床验证中，使用从一项大型研究中获得的尿液样本评估了阳性截定点的敏感性和特异性，该研究测量了美国住院成人放射学确诊 CAP 中由肺炎链球菌血清型引起的比例。
结果
UAD-2 试验被证明具有特异性和可重复性。临床验证表明，针对细菌性肺炎的参考标准，该试验的敏感性和特异性分别为 92.2%和 95.9%。此外，UAD-2 试验在来自美国住院成人的非菌血症性 CAP 病例中确定了 3.72%的肺炎链球菌血清型。当与菌血症性 CAP 病例相结合时，UAD-2 血清型肺炎的比例为 4.33%。
结论
经资格认证/临床验证的 UAD-2 方法适用于了解非菌血症性肺炎链球菌 CAP 的流行病学，以及评估正在开发的未来肺炎球菌结合疫苗的疗效。
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