Immunization with a recombinant BibA surface protein confers immunity and protects mice against group B Streptococcus (GBS) vaginal colonization

Abstract

Streptococcus agalactiae or group B Streptococcus (GBS) is a Gram-positive bacterium divided into ten distinct serotypes that colonizes the vaginal and rectal tracts of approximately 30% of women worldwide. GBS is the leading cause of invasive infection in newborns, causing sepsis, pneumoniae and meningitis. The main strategy to prevent GSB infection in newborns includes the use of intrapartum antibiotic therapy, which does not prevent late-onset diseases and may select resistant bacterial strains. We still do not have a vaccine formulation specific for this pathogen approved for human use. Conserved surface proteins are potential antigens that could be targets for recognition by antibodies and activation of cell opsonization. We used a serotype V GBS (GBS-V)-derived recombinant surface protein, rBibA, and evaluated the potential protective role of the induced antigen-specific antibodies after parenteral or mucosal immunizations in C57BL/6 mice. In vitro and in vivo assays demonstrated that vaccine formulations containing BibA combined with different adjuvants induced serum IgG and/or secreted IgA antibodies, leading to enhanced opsonophagocytosis of GBS-V cells and reduced invasion of epithelial cells. One BibA-based vaccine formulation adjuvanted with a nontoxic derivative of the heat-labile toxin produced by enterotoxigenic Escherichia coli (ETEC) strains was capable of inducing protection against vaginal colonization and lethal parenteral challenge with GBS-V. Serum collected from vaccinated mice conferred passive protection against vaginal colonization in naïve mice challenged with GBS-V. Taken together, the present data demonstrate that the BibA protein is a promising antigen for development of a vaccine to protect against GBS infection.