Sieve analysis: methods for assessing from vaccine trial data how vaccine efficacy varies with genotypic and phenotypic pathogen variation

A key component in the evaluation of efficacy of a vaccine to protect again st disease caused by an antigenically diverse infectious pathogen in a prev entative vaccine trial is assessing how vaccine-induced protection depends on genotypic and phenotypic variations of the exposing pathogen. This asses sment is made by comparing pathogen isolates between infected vaccinated su bjects and infected unvaccinated subjects. A survey of efficacy trial repor ts reveals a lack of systematic, quantitative investigation in this questio n. Analysis tools for testing if vaccine protection against disease is supe rior against some pathogen strains, and for estimating the magnitude of thi s differential vaccine protection, are described. The broad applicability o f the methods is illustrated through analysis of isolates taken from person s infected while participating in vaccine trails for cholera, HIV-1, hepati tis B, rotavirus, and pneumococcus. These analyses reveal intriguing trends for Genentech's monovalent rgp120 HIV-1 vaccine, for two whole-killed-cell oral cholera vaccines, and for other vaccines. (C) 2001 Elsevier Science I nc. All rights reserved.