Finding protective bacterial antigens

Abstract

Current vaccine development efforts are mainly focused on opportunistic pathogens that are frequent colonizers and have complex pathogenesis and interaction with the human host. Therefore, more sophisticated and comprehensive vaccine development approaches have to be considered than for strictly pathogenic bacteria with well-defined virulence mechanisms that typically rely on toxin production. Multigenome analysis and genomic DNA-based screening approaches represent powerful strategies for identifying proteinaceous vaccine candidates. The two approaches we review here are the reverse vaccinology and the ANTIGENome technologies that have been applied for numerous human pathogens and resulted in clinical vaccine candidates. In both cases, the primary selections—that are based on in silico prediction or human antibody response, respectively—are complemented with a series of in vitro assays to preselect vaccine candidates for testing in animal models of efficacy to ultimately single out the vaccine antigens destined to move into development. When applied to the same pathogen, the two approaches appear to identify overlapping pools of antigens that not completely superimpose, suggesting that the methods might complement each other. Importantly, the conclusions from the application of two technologies are similar: Broadly protective antigens rarely exist, and combination of several protein antigens is necessary for the development of universal vaccines.