A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections

Youssouf Sereme1, Cécile Schrimp1, Helène Faury1,2

  • 1Université Paris Cité, CNRS, INSERM, Institut Necker Enfants Malades, Paris, France.

Nature Communications
|April 8, 2024
PubMed

Insights

A live attenuated vaccine candidate protects newborn mice against E. coli K1 infections. Maternal immunization transfers protective antibodies to pups, offering a potential strategy against neonatal bacterial infections and preterm birth complications.

Area of Science:

  • Neonatal immunology
  • Vaccine development
  • Microbiology

Background:

  • Preterm birth is a leading cause of neonatal mortality.
  • Escherichia coli, particularly E. coli K1 strains, are common causes of severe neonatal bacterial infections.
  • Women with a history of preterm delivery face a high risk of recurrence.

Purpose of the Study:

  • To evaluate the immunological, microbiological, and protective properties of a live attenuated vaccine candidate against E. coli neonatal infections.
  • To assess the efficacy of maternal immunization and antibody transfer in protecting newborn pups.

Main Methods:

  • Characterization of a live attenuated E. coli K1 E11 ∆aroA vaccine candidate in adult female mice and their pups.
  • Immunization of mothers prior to mating, followed by challenge with K1 and non-K1 E. coli strains.
  • Assessment of maternal antibody transfer and pup protection against neonatal meningitis models.

Main Results:

  • The E. coli K1 E11 ∆aroA vaccine induced strong immunity characterized by polyclonal bactericidal antibodies.
  • Immunized mothers successfully transferred protective antibodies to their pups.
  • Newborn mice receiving maternal antibodies were protected against diverse K1 and non-K1 E. coli strains.

Conclusions:

  • The study provides preclinical proof of concept for a live attenuated vaccine against severe E. coli infections.
  • This vaccine strategy targets women at risk of preterm delivery, addressing a critical unmet medical need.
  • Maternal immunization offers a promising approach to prevent neonatal E. coli infections and associated mortality.