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

Author

Listed:
  • Youssouf Sereme

    (Institut Necker Enfants Malades)

  • Cécile Schrimp

    (Institut Necker Enfants Malades)

  • Helène Faury

    (Institut Necker Enfants Malades
    University de Paris)

  • 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
    Maternité Port-Royal)

  • Stephane Bonacorsi

    (Université Paris Cité
    AP-HP)

  • David Skurnik

    (Institut Necker Enfants Malades
    University de Paris
    Maternité Port-Royal)

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.

Suggested Citation

  • Youssouf Sereme & Cécile Schrimp & Helène Faury & Maeva Agapoff & Esther Lefebvre-Wloszczowski & Yunhua Chang Marchand & Elisabeth Ageron-Ardila & Emilie Panafieu & Frank Blec & Mathieu Coureuil & Eri, 2024. "A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46775-x
    DOI: 10.1038/s41467-024-46775-x
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    References listed on IDEAS

    as
    1. Sergio Arredondo-Alonso & George Blundell-Hunter & Zuyi Fu & Rebecca A. Gladstone & Alfred Fillol-Salom & Jessica Loraine & Elaine Cloutman-Green & Pål J. Johnsen & Ørjan Samuelsen & Anna K. Pöntinen , 2023. "Evolutionary and functional history of the Escherichia coli K1 capsule," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Chao Shan & Antonio E. Muruato & Brett W. Jagger & Justin Richner & Bruno T. D. Nunes & Daniele B. A. Medeiros & Xuping Xie & Jannyce G. C. Nunes & Kaitlyn M. Morabito & Wing-Pui Kong & Theodore C. Pi, 2017. "A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    3. Chao Shan & Xuping Xie & Huanle Luo & Antonio E. Muruato & Yang Liu & Maki Wakamiya & Jun-Ho La & Jin Mo Chung & Scott C. Weaver & Tian Wang & Pei-Yong Shi, 2019. "Maternal vaccination and protective immunity against Zika virus vertical transmission," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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