Despite the dramatic increase in antimicrobial resistance, there is a dearth of antibiotics in development and few pharmaceutical companies working in the field. Further, any new antibiotics are likely to have a short shelf life. Ab-based interventions offer alternatives that are not likely to be circumvented by the widely prevalent antibiotic resistance genes. Bovine colostrum (BC)—the first milk after parturition, rich in nutrients and immune components—promotes gut integrity and modulates the gut microbiome. We developed a hyperimmune BC (HBC) enriched in Abs to a highly conserved LOS core region of Gram-negative bacteria by immunizing pregnant cows with a vaccine comprised of detoxified LOS from Escherichia coli O111 Rc (J5) mutant non-covalently complexed to group B meningococcal outer membrane protein (J5dLOS/OMP). This vaccine generated robust levels of anti-J5 LOS Ab in the colostrum. When given orally to neutropenic rats challenged orally with Pseudomonas aeruginosa, administration of HBC improved survival compared to non-immune rats, while both BC preparations improved survival compared to PBS controls. Elevated circulating endotoxin levels correlated with mortality. HBC and to a lesser extent non-immune BC reduced bacterial burden from the liver, lung, and spleen. We conclude that HBC and to a lesser extent BC may be effective supplements that improve outcome from lethal gut-derived disseminated infection and may reduce transmission of Gram-negative bacilli from the gastrointestinal tract.

尽管抗菌素耐药性急剧增加，但开发中的抗生素仍然匮乏，而且从事该领域工作的制药公司也很少。此外，任何新抗生素的保质期都可能很短。基于抗体的干预措施提供了不可能被广泛流行的抗生素抗性基因规避的替代方案。牛初乳 (BC) 是产后的第一口乳汁，富含营养成分和免疫成分，可促进肠道完整性并调节肠道微生物群。我们通过使用由大肠杆菌O111 Rc (J5) 突变体的解毒 LOS 与 B 组非共价复合而成的疫苗对怀孕奶牛进行免疫接种，开发了一种富含革兰氏阴性菌高度保守的 LOS 核心区域抗体的超免疫 BC (HBC)。脑膜炎球菌外膜蛋白（J5dLOS/OMP）。该疫苗在初乳中产生了高水平的抗 J5 LOS 抗体。当口服铜绿假单胞菌攻击的中性粒细胞减少大鼠时，与非免疫大鼠相比，给予 HBC 可以提高存活率，而与 PBS 对照相比，两种 BC 制剂都可以提高存活率。循环内毒素水平升高与死亡率相关。 HBC 和较小程度的非免疫 BC 减少了肝脏、肺和脾脏的细菌负荷。我们的结论是，HBC 和较小程度上的 BC 可能是有效的补充剂，可以改善致命性肠道源性播散性感染的结果，并可以减少革兰氏阴性杆菌从胃肠道的传播。