Efficacious vaccination needs to confer protection against the vast majority of pathogens capable of causing a particular disease. Development of such vaccines is hindered by the great variability of microbes. Most pathogens have evolved variants that are able to express non-uniform surface structures. Naturally, evolutionary pressure has selected the most immunogenic antigens to be the most versatile. A combination of these multiform surface antigens forms the basis of classification of microbes into serotypes. Unfortunately, immune response in most cases is serotype-dependent, i.e. cross-protection among serotypes/serogroups of a given pathogen is limited. This review focuses on the strategies used for the engineering of broad-protective vaccine candidates, i.e., vaccines that induce a global, serotype-independent protection. The most plausible approach is to immunize with a multivalent vaccine containing different serotypes or purified serotype-determining antigens of a given pathogen. This arrangement is, however, efficient only against those microbes that have a limited number of serotypes, or few serotypes are responsible for the majority of the infections. Instead of using multivalent vaccine cocktails, cross-protective capacity of vaccine strains could be improved by making the conserved (i.e., shared by all variants) antigens more immunogenic. Elimination or down-regulation of the non-uniform antigens may increase immunogenicity of conserved minor antigens in vaccine candidates. Alternatively, shared antigens might be over-expressed in homologous or heterologous attenuated strains. Finally, purified conserved antigens could be used as subunit vaccines. In this paper, advantages and drawbacks of several such approaches will be reviewed. (C) 2008 Elsevier GrnbH. All rights reserved.
