PDF(Pubmed)
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.
摘要：
早产是目前新生儿发病和死亡的主要原因。遗传,怀疑是免疫和感染原因。早产儿有更高的风险严重的细菌新生儿感染,其中大部分是由大肠杆菌，特别是大肠杆菌K1菌株引起的。具有早产史的妇女具有高的复发风险,因此构成开发针对大肠杆菌新生儿感染的疫苗的目标人群。这里,我们描述了免疫学，在大肠杆菌K1和非K1菌株攻击后，成年雌性小鼠及其幼崽的减毒活疫苗候选物的微生物学和保护特性。我们的结果表明，大肠杆菌K1E11ΔaroA疫苗诱导强大的免疫力，由多克隆杀菌抗体驱动。在我们的脑膜炎模型中,在交配前进行免疫接种的母亲将母体抗体转移给幼崽，它保护新生小鼠免受大肠杆菌的各种K1和非K1菌株的侵害。考虑到很高的死亡率和与新生儿大肠杆菌K1脑膜炎相关的神经系统后遗症，我们的结果为在有早产风险的女性中开发针对严重大肠杆菌感染的减毒活疫苗的概念提供了临床前证据.
