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Preterm 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.

T cell-mediated graft rejection is mostly correlated with potent Th1 responses. However, because IFNγ mice reject their graft as efficiently as wild-type (WT) mice, the exact contribution of IFNγ and its transcription factor T-bet remains a matter of debate. Here, we address this question in the context of pancreatic islet allograft to better inform the molecular pathways that hampers islet survival in vivo.Pancreatic islets from BALB/c mice were transplanted in WT, IFNγ, or T-bet C57BL/6 mice. Graft survival and the induction of effector and cytotoxic T-cell responses were monitored.Rejection of fully mismatched islet allografts correlated with high expression of both IFNγ and T-bet in WT recipients. However, allogeneic islets were permanently accepted in T-bet mice, in contrast to IFNγ hosts. Long-term survival correlated with decreased CD4 and CD8 T-cell infiltrates, drastically reduced donor-specific IFNγ and tumor necrosis factor tumor necrosis factor α responses and very low expression of the cytotoxic markers granzyme B, perforin, and FasLigand. In addition, in vitro and in vivo data pointed to an increased susceptibility of T-bet CD8 T cell to apoptosis. These observations were not reported in IFNγ mice, which have set up compensatory effector mechanisms comprising an increased expression of the transcription factor Eomes and cytolytic molecules as well as tumor necrosis factor α-mediated but not IL-4 nor IL-17-mediated allogeneic responses.Anti-islet T-cell responses require T-bet but not IFNγ-dependent programs. Our results provide new clues on the mechanisms dictating islet rejection and may help refine the therapeutic/immunosuppressive regimens applied in diabetic patients receiving islets or pancreas allografts.