Pre-clinical in vitro and in vivo characterization of a maternal vaccination before conception to protect against severe neonatal infections caused byEscherichia coliK1

Abstract

AbstractPreterm birth remains the leading cause of neonatal morbidity and mortality today. Genetic, immunological, and infectious substrates are suspected. Preterm infants are at higher risk of severe neonatal infections and the main cause of bacterial infection in this population isEscherichia coliK1. Unfortunately, women with history of preterm birth have a high risk of recurrence. Therefore, these women constitute a target population for a vaccine, to date non-existent, againstE. coliK1 to prevent these infections.In this study, we characterize the immunological and microbiological properties in adult female mice of a live attenuated vaccine candidate and the protection it conferred to newborn mice against severe infection caused byE. coliK1. We show that ourE. coliK1 ΔaroA vaccine induces a strong immunity driven by polyclonal bactericidal antibodies. In our model of meningitis, pups born from mothers immunized before conception were strongly protected against different strains ofE. coliK1 both in early-onset and late-onset diseases.Given the very high rate of mortality and neurological sequalae in neonatal meningitis caused byE. coliK1, this pre-clinical study provides a proof-of-concept for the development of a vaccine strategy againstE. coliK1 severe infection in women at risk of preterm birth.