Use of a Whole Genome Approach To Identify Vaccine Molecules Affording Protection against <i>Streptococcus pneumoniae</i> Infection

TLDR

Microbial targets for protective humoral immunity are typically surface‑localized proteins that contain common secretion or surface‑binding motifs. Using the whole‑genome sequence of *Streptococcus pneumoniae*, the authors identified 130 open reading frames encoding proteins with secretion motifs or similarity to predicted virulence factors. Immunization of mice with 108 candidate proteins identified from the genome revealed six antigens that protected against disseminated infection, were surface‑localized, broadly distributed across strains, and immunogenic in humans, validating the genomic strategy and suggesting these antigens could improve *S.

Abstract

Microbial targets for protective humoral immunity are typically surface-localized proteins and contain common sequence motifs related to their secretion or surface binding. Exploiting the whole genome sequence of the human bacterial pathogen Streptococcus pneumoniae, we identified 130 open reading frames encoding proteins with secretion motifs or similarity to predicted virulence factors. Mice were immunized with 108 of these proteins, and 6 conferred protection against disseminated S. pneumoniae infection. Flow cytometry confirmed the surface localization of several of these targets. Each of the six protective antigens showed broad strain distribution and immunogenicity during human infection. Our results validate the use of a genomic approach for the identification of novel microbial targets that elicit a protective immune response. These new antigens may play a role in the development of improved vaccines against S. pneumoniae.