Streptococcus mutans glutamate binding protein (GlnH) as antigen target for a mucosal anti-caries vaccine.

BACKGROUND: In recent years, several studies have demonstrated that bacterial ABC transporters present relevant antigen targets for the development of vaccines against bacteria such as Streptococcus pneumoniae and Enterococcus faecalis. In Streptococcus mutans, the glutamate transporter operon (glnH), encoding an ABC transporter, is associated with acid tolerance and represents an important virulence-associated factor for the development of dental caries. RESULTS: In this study, we generated a recombinant form of the S. mutans GlnH protein (rGlnH) in Bacillus subtilis. Mice immunized with this protein antigen elicited strong antigen-specific antibody responses after sublingual administration of a vaccine formulation containing a mucosal adjuvant, a non-toxic derivative of the heat-labile toxin (LTK63) originally produced by enterotoxigenic Escherichia coli (ETEC) strains. Serum anti-rGlnH antibodies reduced adhesion of S. mutans to the oral cavity of naïve mice. Moreover, mice actively immunized with rGlnH were partially protected from oral colonization after exposure to the S. mutans NG8 strain. CONCLUSIONS: Our results indicate that S. mutans rGlnH is a potential target antigen capable of inducing specific and protective antibody responses after immunization. Overall, these observations raise the prospect of the development of mucosal anti-caries vaccines.

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

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.