BACKGROUND:The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile. METHODS AND FINDINGS:We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible. CONCLUSIONS:In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.

译文

背景:禽流感最近在野生鸟类和家禽中的传播可能是1918年人类大流行病出现的先兆。因此,正在考虑人类大流行前疫苗的库存(针对禽类)。对于许多国家而言,这些疫苗库存的主要限制因素是维持的抗原总量。我们测试了以下假设:较低的单个剂量(即小于建议的最大保护剂量)可能会提供实质性的社区级额外好处,因为对于给定的抗原库总体积,它们将允许更广泛的疫苗覆盖范围。
方法和发现:我们使用数学模型来预测不同策略下的感染发作率。该模型结合了个体对不同剂量疫苗接种的反应以及大流行性流感的人际传播过程。我们发现,如果以较低的剂量向更多的人注射疫苗,则可能会大大降低发作率。这些结果适用于可获得数据的所有三种候选疫苗。作为影响程度的指导,我们根据免疫原性的历史研究模拟了流行病。例如,对于一种可获得数据的疫苗,如果给美国3亿总人口中的160人提供最佳剂量,而不是给3亿人中的20人给予最佳剂量,那么其发作率将从67.6%降至58.7%。最大保护剂量(如美国国家大流行防备计划所公布)。关于疫苗保护的确切性质的许多替代假设,我们的结果是保守的。我们还考虑了一个模型变体,其中包括代表儿童的单个高风险亚组。对于允许以最佳剂量仅向高危人群提供疫苗的较小库存,即使存在高危人群,使用均质模型的预期收益也会在低危人群中形成较低的界限传染性和易感性的两倍。
结论:除了个人层面的保护(即疫苗效力)外,在决定储存量和剂量时还应考虑大流行前疫苗计划在人群层面的影响。我们的结果表明,可以采用较低的疫苗剂量以增加人群覆盖率,从而降低总体感染率。

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