Cherry J D, Gornbein J, Heininger U, Stehr K
Department of Pediatrics, University of California, Los Angeles, School of Medicine, USA.
Vaccine. 1998 Dec;16(20):1901-6. doi: 10.1016/s0264-410x(98)00226-6.
In a pertussis vaccine efficacy trial in Germany we collected sera from vaccinees (DTaP or DTP) after the third and fourth doses of vaccine or at comparable time periods in DT vaccine recipients. In addition, sera were collected from a randomized sample of subjects in each vaccine group at approximately 3-month intervals from which antibody kinetic curves were constructed, which allowed us to estimate specific antibody values to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin and fimbriae-2 at the time of exposure in the household setting. The imputed geometric mean antibody values to PT, pertactin and fimbriae-2 at the time of household exposure to Bordetella pertussis infection were higher (p < 0.07 or lower) in non-cases compared with cases. A multivariate (classification tree) analysis found that only pertactin and PT were significant in protection. Subjects with an imputed pertactin value of < 7 EU ml-1 had a 67% (18/27) chance of infection regardless of the PT value. If the pertactin value was > or = 7 EU ml-1 and the PT value > or = 66 EU ml-1 all subjects were non-cases. If the pertactin value was > or = 7 and the PT value was < 66 EU ml-1 the predicted probability of being a case was 31% (15/49). Logistic regression analysis also found that high versus low pertactin values were associated with illness prevention following household exposure. In the presence of antibody to pertactin, PT and fimbriae-2, the additional presence of antibody to FHA did not contribute to protection. Our data support historical data indicating that agglutinating antibodies are associated with protection and also recent serologic correlates data and clinical efficacy data which indicate that multicomponent vaccines containing pertactin and fimbriae have better efficacy than PT or PT/FHA vaccines.
在德国进行的一项百日咳疫苗效力试验中，我们在第三剂和第四剂疫苗接种后或在DT疫苗接种者的相应时间段采集了疫苗接种者（DTaP或DTP）的血清。此外，从每个疫苗组的随机样本中大约每隔3个月采集一次血清，据此构建抗体动力学曲线，从而使我们能够估计在家庭环境暴露时针对百日咳毒素（PT）、丝状血凝素（FHA）、百日咳杆菌黏附素和2型菌毛的特异性抗体值。与病例相比，家庭暴露于百日咳博德特氏菌感染时，非病例中PT、百日咳杆菌黏附素和2型菌毛的推算几何平均抗体值更高（p<0.07或更低）。多变量（分类树）分析发现，只有百日咳杆菌黏附素和PT在保护作用方面具有显著性。推算的百日咳杆菌黏附素值<7 EU/ml的受试者，无论PT值如何，感染几率为67%（18/27）。如果百日咳杆菌黏附素值≥7 EU/ml且PT值≥66 EU/ml，则所有受试者均为非病例。如果百日咳杆菌黏附素值≥7且PT值<66 EU/ml，成为病例的预测概率为31%（15/49）。逻辑回归分析还发现，家庭暴露后，百日咳杆菌黏附素高值与低值与疾病预防相关。在存在针对百日咳杆菌黏附素、PT和2型菌毛的抗体时，额外存在针对FHA的抗体对保护作用没有贡献。我们的数据支持了表明凝集抗体与保护作用相关的既往数据，以及表明含百日咳杆菌黏附素和菌毛的多组分疫苗比PT或PT/FHA疫苗具有更好效力的近期血清学相关数据和临床效力数据。
