Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study
Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study
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DOI：
10.1016/s1473-3099(14)70822-9
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发表时间：
2014-09-01
影响因子：
56.3
通讯作者：
Goldblatt, David
中科院分区：
文献类型：
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作者：
Andrews, Nick J.;Waight, Pauline A.;Goldblatt, David
背景 13 价肺炎球菌结合疫苗 (PCV13) 的功效是在获得许可之前根据为七价疫苗 (PCV7) 建立的保护的总体相关性推断的。我们在英格兰、威尔士和北爱尔兰对血清型特异性疫苗的有效性和免疫原性进行了许可后评估，以获得对个体血清型的保护的相关性。方法我们使用间接队列方法评估了针对侵袭性肺炎球菌疾病的疫苗有效性。我们测量了婴儿接受两次初次剂量的 PCV7 (n=126) 或 PCV13 (n=237) 后的血清型特异性 IgG 浓度，以及这些婴儿子集 (n=100) 的调理吞噬抗体滴度。我们通过将保护百分比与同等百分比的婴儿达到的阈值抗体浓度相关联，得出了保护的相关性。我们使用多变量逻辑回归来估计疫苗有效性，并使用反向累积分布曲线来估计保护的相关性。 结果 对于研究中纳入的 706 例侵袭性肺炎球菌疾病病例，12 个月前接种两剂或 12 个月后接种一剂后 PCV13 疫苗的有效性为 75% (95% CI 58-84)。 PCV7 血清型的疫苗有效性为 90% (34-98)，PCV13 中其他六种血清型的疫苗有效性为 73% (55-84)。对另外六种 PCV13 血清型中的四种显示出保护作用（疫苗对血清型 3 的有效性不显着，并且在观察期间没有发生血清型 5 感染病例）。 PCV13 和 PCV7 的疫苗有效性低于许可期间使用的 0-35 μg/mL 保护的总体相关性所预测的。计算出的血清型特异性保护相关性对于血清型1、3、7F、19A、19F高于0.35μg/mL，对于血清型6A、6B、18C和23F低于0.35μg/mL。调理吞噬抗体滴度为八分之一或更高并不能预测保护作用。解释 PCV13 为大多数疫苗血清型提供显着的保护作用。尽管使用 0-35 μg/mL 的总体保护相关性已经能够获得有效的新 PCV 许可，但血清型特异性保护相关性差异很大。需要更好地了解启动后 IgG 浓度与长期保护之间的关系。
Background Efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) was inferred before licensure from an aggregate correlate of protection established for the seven-valent vaccine (PCV7). We did a postlicensure assessment of serotype-specific vaccine effectiveness and immunogenicity in England, Wales, and Northern Ireland to derive the correlates of protection for individual serotypes.Methods We assessed vaccine effectiveness against invasive pneumococcal disease using the indirect cohort method. We measured serotype-specific IgG concentration in infants after they were given two priming doses of PCV7 (n=126) or PCV13 (n=237) and opsonophagocytic antibody titre from a subset of these infants (n=100). We derived correlates of protection by relating percentage protection to a threshold antibody concentration achieved by an equivalent percentage of infants. We used multivariable logistic regression to estimate vaccine effectiveness and reverse cumulative distribution curves to estimate correlates of protection.Findings For the 706 cases of invasive pneumococcal disease included in the study, PCV13 vaccine effectiveness after two doses before age 12 months or one dose from 12 months was 75% (95% CI 58-84). Vaccine effectiveness was 90% (34-98) for the PCV7 serotypes and 73% (55-84) for the six additional serotypes included in PCV13. Protection was shown for four of the six additional PCV13 serotypes (vaccine effectiveness for serotype 3 was not significant and no cases of serotype 5 infection occurred during the observation period). The vaccine effectiveness for PCV13 and PCV7 was lower than predicted by the aggregate correlate of protection of 0-35 mu g/mL used during licensing. Calculated serotype-specific correlates of protection were higher than 0.35 mu g/mL for serotypes 1,3,7F, 19A, 19F, and lower than 0.35 mu g/mL for serotypes 6A, 6B, 18C, and 23F. Opsonophagocytic antibody titres of 1 in 8 or higher did not predict protection.Interpretation PCV13 provides significant protection for most of the vaccine serotypes. Although use of the aggregate correlate of protection of 0-35 mu g/mL has enabled the licensing of effective new PCVs, serotype-specific correlates of protection vary widely. The relation between IgG concentration after priming and long-term protection needs to be better understood.