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Non-Invasive Model of Neuropathogenic Escherichia coli Infection in the Neonatal Rat
Published on: October 29, 2014
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.
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.
Abstract:
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 characterize 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, mothers immunized prior to mating transfer maternal antibodies to pups, which protect newborn mice 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.

