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

Youssouf Sereme, Cécile Schrimp, Helène Faury, Maeva Agapoff, Esther Lefebvre-Wloszczowski, Yunhua Chang Marchand, Elisabeth Ageron-Ardila, Emilie Panafieu, Frank Blec, Mathieu Coureuil, Eric Frapy, Vassilis Tsatsaris, Stephane Bonacorsi and David Skurnik ()
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Youssouf Sereme: Institut Necker Enfants Malades
Cécile Schrimp: Institut Necker Enfants Malades
Helène Faury: Institut Necker Enfants Malades
Maeva Agapoff: Institut Necker Enfants Malades
Esther Lefebvre-Wloszczowski: Institut Necker Enfants Malades
Yunhua Chang Marchand: Institut Necker Enfants Malades
Elisabeth Ageron-Ardila: Institut Necker Enfants Malades
Emilie Panafieu: LEAT antenne Imagine- SFR Necker INSERM US 24
Frank Blec: LEAT antenne Imagine- SFR Necker INSERM US 24
Mathieu Coureuil: Institut Necker Enfants Malades
Eric Frapy: Institut Necker Enfants Malades
Vassilis Tsatsaris: AP-HP
Stephane Bonacorsi: Université Paris Cité
David Skurnik: Institut Necker Enfants Malades

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-46775-x

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