Group B Streptococcus (GBS) is the leading cause of neonatal
pneumonia,
septicemia, and
meningitis. We have previously shown that in adult mice GBS glycolytic
enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular
virulence factor that induces production of the immunosuppressive
cytokine interleukin-10 (IL-10) by the host early upon
bacterial infection. Here, we investigate whether immunity to neonatal GBS
infection could be achieved through maternal vaccination against bacterial GAPDH. Female BALB/c mice were immunized with rGAPDH and the progeny was infected with a lethal inoculum of GBS strains. Neonatal mice born from mothers immunized with rGAPDH were protected against
infection with GBS strains, including the ST-17 highly virulent clone. A similar protective effect was observed in newborns passively immunized with anti-rGAPDH
IgG antibodies, or F(ab')(2) fragments, indicating that protection achieved with rGAPDH vaccination is independent of opsonophagocytic killing of bacteria. Protection against lethal GBS
infection through rGAPDH maternal vaccination was due to neutralization of
IL-10 production soon after
infection. Consequently,
IL-10 deficient (IL-10(-/-)) mice pups were as resistant to GBS
infection as pups born from vaccinated mothers. We observed that protection was correlated with increased neutrophil trafficking to infected organs. Thus, anti-rGAPDH or anti-IL-10R treatment of mice pups before GBS
infection resulted in increased neutrophil numbers and lower bacterial load in infected organs, as compared to newborn mice treated with the respective control
antibodies. We showed that mothers immunized with rGAPDH produce
neutralizing antibodies that are sufficient to decrease
IL-10 production and induce neutrophil recruitment into infected tissues in newborn mice. These results uncover a novel mechanism for GBS virulence in a neonatal host that could be neutralized by vaccination or
immunotherapy. As GBS GAPDH is a structurally conserved
enzyme that is metabolically essential for bacterial growth in media containing
glucose as the sole
carbon source (i.e., the blood), this
protein constitutes a powerful candidate for the development of a human
vaccine against this pathogen.