Natural immune boosting in pertussis dynamics and the potential for long-term vaccine failure
Natural immune boosting in pertussis dynamics and the potential for long-term vaccine failure
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DOI：
10.1073/pnas.1014394108
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发表时间：
2011-04-26
影响因子：
11.1
通讯作者：
Bjornstad, Ottar N.
中科院分区：
文献类型：
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作者：
Lavine, Jennie S.;King, Aaron A.;Bjornstad, Ottar N.
百日咳的发病率，不像许多其他儿童疾病，有一个有效的疫苗，一直在增加，在过去的二十年，尽管高水平的疫苗覆盖率。它的重新出现在青少年和成年人中特别明显。已经提出了许多假设来解释这两种模式，但对免疫力持续时间有限的临床数据与疫苗接种前和疫苗接种后年龄特异性发病率进行简约的调和仍然是一个挑战。我们认为免疫学相关，但流行病学很大程度上被忽视的可能性，一个启动的免疫系统可以响应较低剂量的抗原比一个幼稚的。我们假设，在前疫苗时代，青少年和成年人的引发免疫力经常通过再次暴露而增强，因此在面临潜在侵蚀个体免疫力的情况下保持群体免疫力。相比之下，除了流行病爆发期间，目前病原体循环较低，使得免疫力在再次暴露发生之前丧失。我们开发并分析了一个包含这一假设的年龄结构模型。我们发现，免疫增强必须比原发性感染更容易触发，以解释年龄发病率数据。我们通过分叉分析和模拟进行特定年龄的动态预测。这里提出的增强模型粗略地捕捉了来自高度接种疫苗国家的百日咳数据的四个关键特征：（i）年龄特异性发病率的变化，（ii）在高疫苗覆盖率下重新出现，（iii）在疫苗接种前和后时期可能出现周期性动态，和（iv）从易感染-感染-恢复（SIR）-样到易感染-感染-恢复-易感（SIRS）-样的明显转变。比如百日咳杆菌的感染和免疫现象。
Incidence of whooping cough, unlike many other childhood diseases for which there is an efficacious vaccine, has been increasing over the past twenty years despite high levels of vaccine coverage. Its reemergence has been particularly noticeable among teenagers and adults. Many hypotheses have been put forward to explain these two patterns, but parsimonious reconciliation of clinical data on the limited duration of immunity with both pre- and postvaccine era age-specific incidence remains a challenge. We consider the immunologically relevant, yet epidemiologically largely neglected, possibility that a primed immune system can respond to a lower dose of antigen than a naive one. We hypothesize that during the prevaccine era teenagers' and adults' primed immunity was frequently boosted by reexposure, so maintaining herd immunity in the face of potentially eroding individual immunity. In contrast, low pathogen circulation in the current era, except during epidemic outbreaks, allows immunity to be lost before reexposure occurs. We develop and analyze an age-structured model that encapsulates this hypothesis. We find that immune boosting must be more easily triggered than primary infection to account for age-incidence data. We make age-specific and dynamical predictions through bifurcation analysis and simulation. The boosting model proposed here parsimoniously captures four key features of pertussis data from highly vaccinated countries: (i) the shift in age-specific incidence, (ii) reemergence with high vaccine coverage, (iii) the possibility for cyclic dynamics in the pre- and postvaccine eras, and (iv) the apparent shift from susceptible-infectious-recovered (SIR)-like to susceptible-infectious-recovered-susceptible (SIRS)-like phenomenology of infection and immunity to Bordetella pertussis.