Project description:Preterm birth is currently the leading cause of neonatal morbidity and mortality. Genetic, immunological and infectious causes are suspected. Preterm infants have a higher risk of severe bacterial neonatal infections, most of which are caused by Escherichia coli an in particular E. coli K1strains. Women with history of preterm delivery have a high risk of recurrence and therefore constitute a target population for the development of vaccine against E. coli neonatal infections. Here, we characterized the immunological, microbiological and protective properties of a live attenuated vaccine candidate in adult female mice and their pups against after a challenge by K1 and non-K1 strains of E. coli. Our results show that the E. coli K1 E11 aroA vaccine induces strong immunity, driven by polyclonal bactericidal antibodies. In our model of meningitis, pups born to mothers immunized before mating were well protected against various K1 and non-K1 strains of E. coli. Given the very high mortality rate and the neurological sequalae associated with neonatal E. coli K1 meningitis, our results constitute preclinical proof of concept for the development of a live attenuated vaccine against severe E. coli infections in women at risk of preterm delivery.
Project description:Neonatal meningitis and neurocomplications are often a complication of neonatal bacterial bloodstream infections. As distinct bacterial organisms may cause different disease outcomes, we assessed two separate bacterial infections: E. coli and S. agalactiae (GBS). In this study we assessed differences in immune response within the brain tissue of neonates and the effect of gamma delta T cells to the brain during bacterial infection. As gamma delta T cells are resident to tissues, and can contribute to bacterial infections, we compared wild-type and TCRdKO mice, which lack gamma delta T cells, in two infections models: E. coli and GBS.
