Strategies for the development of vaccines conferring broad-spectrum protection.

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.