ABSTRACT
Group B Streptococcus (GBS) is a multiserotype bacterial pathogen representing a major cause of life-threatening infections in newborns. To develop a broadly protective vaccine, we analyzed the genome sequences of eight GBS isolates and cloned and tested 312 surface proteins as vaccines. Four proteins elicited protection in mice, and their combination proved highly protective against a large panel of strains, including all circulating serotypes. Protection also correlated with antigen accessibility on the bacterial surface and with the induction of opsonophagocytic antibodies. Multigenome analysis and screening described here represent a powerful strategy for identifying potential vaccine candidates against highly variable pathogens.
Subject(s)
Antigens, Bacterial/immunology , Genome, Bacterial , Streptococcal Infections/prevention & control , Streptococcal Vaccines/immunology , Streptococcus agalactiae/genetics , Streptococcus agalactiae/immunology , Animals , Animals, Newborn , Antibodies, Bacterial/biosynthesis , Antigens, Bacterial/genetics , Antigens, Surface/genetics , Antigens, Surface/immunology , Bacterial Proteins/immunology , Computational Biology , Female , Humans , Immunity, Maternally-Acquired , Mice , Neutrophils/immunology , Opsonin Proteins , Phagocytosis , Serotyping , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Streptococcus agalactiae/classification , VaccinationABSTRACT
The 2,160,267 bp genome sequence of Streptococcus agalactiae, the leading cause of bacterial sepsis, pneumonia, and meningitis in neonates in the U.S. and Europe, is predicted to encode 2,175 genes. Genome comparisons among S. agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and the other completely sequenced genomes identified genes specific to the streptococci and to S. agalactiae. These in silico analyses, combined with comparative genome hybridization experiments between the sequenced serotype V strain 2603 V/R and 19 S. agalactiae strains from several serotypes using whole-genome microarrays, revealed the genetic heterogeneity among S. agalactiae strains, even of the same serotype, and provided insights into the evolution of virulence mechanisms.
