Center for Vaccine Development and Global Health, University of Maryland School of Medicine, USA.
Division of Infectious Diseases, Rhode Island Hospital, USA.
Innate Immun. 2021 Apr;27(3):266-274. doi: 10.1177/17534259211007538.
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 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 , 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.
尽管抗菌药物耐药性急剧增加，但可供开发的抗生素却很少，从事该领域的制药公司也寥寥无几。此外，任何新的抗生素都可能寿命短暂。AB 类干预措施提供了替代方案，不太可能被广泛存在的抗生素耐药基因规避。牛初乳（BC）——分娩后最初的乳汁，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组。我们通过用含有源自 O111 Rc（J5）突变体的已解毒 LOS 与 B 群脑膜炎球菌外膜蛋白（J5dLOS/OMP）非共价复合的疫苗免疫怀孕奶牛，开发了富含针对革兰氏阴性菌 LOS 核心区域高度保守区域的抗体的高免疫牛初乳（HBC）。该疫苗在牛初乳中产生了针对 J5 LOS 的强大抗抗体水平。当给予中性粒细胞减少的大鼠口服口服挑战时，与非免疫大鼠相比，HBC 给药可提高存活率，而 BC 制剂均可提高存活率与 PBS 对照组相比。循环内毒素水平升高与死亡率相关。HBC 和在较小程度上非免疫 BC 可降低来自肝脏，肺和脾脏的细菌负荷。我们得出的结论是，HBC 和在较小程度上 BC 可能是有效的补充剂，可以改善从致命的肠道来源的播散性感染的结果，并可能减少来自胃肠道的革兰氏阴性杆菌的传播。
