Benkeser David, Juraska Michal, Gilbert Peter B
Department of Biostatistics and Bioinformatics, Emory University; 1518 Clifton Rd. NE; Atlanta, GA USA 30322.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center; 1100 Fairview Ave. N; Seattle, WA USA 98109.
J Soc Fr Statistique (2009). 2020 Jul;161(1):164-175.
Preventive vaccines are an effective public health intervention for reducing the burden of infectious diseases, but have yet to be developed for several major infectious diseases. Vaccine sieve analysis studies whether and how the efficacy of a vaccine varies with the genetics of the infectious pathogen, which may help guide future vaccine development and deployment. A standard statistical approach to sieve analysis compares the effect of the vaccine to prevent infection and disease caused by pathogen types defined dichotomously as genetically near or far from a reference pathogen strain inside the vaccine construct. For example, near may be defined by amino acid identity at all amino acid positions considered in a multiple alignment and far defined by at least one amino acid difference. An alternative approach is to study the efficacy of the vaccine as a function of genetic distance from a pathogen to a reference vaccine strain where the distance cumulates over the set of amino acid positions. We propose a nonparametric method for estimating and testing the trend in the effect of a vaccine across genetic distance. We illustrate the operating characteristics of the estimator via simulation and apply the method to a recent preventive malaria vaccine efficacy trial.
预防性疫苗是减轻传染病负担的一种有效公共卫生干预措施，但针对几种主要传染病的疫苗尚未研发出来。疫苗筛选分析研究疫苗效力是否以及如何随传染性病原体的基因变化，这可能有助于指导未来疫苗的研发和应用。一种用于筛选分析的标准统计方法是比较疫苗对预防由病原体类型引起的感染和疾病的效果，这些病原体类型被二分定义为在疫苗构建体中与参考病原体菌株在基因上接近或远离。例如，接近可以通过多重比对中考虑的所有氨基酸位置的氨基酸同一性来定义，而远则由至少一个氨基酸差异来定义。另一种方法是研究疫苗效力作为从病原体到参考疫苗菌株的遗传距离的函数，其中距离在氨基酸位置集合上累积。我们提出一种非参数方法来估计和检验疫苗效果在遗传距离上的趋势。我们通过模拟说明了估计器的操作特征，并将该方法应用于最近的预防性疟疾疫苗效力试验。
