Microbiology Hub Kericho, KEMRI-USAMRD-A/Kenya, Kericho, Kenya.
Department of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
mSphere. 2022 Jun 29;7(3):e0102021. doi: 10.1128/msphere.01020-21. Epub 2022 May 25.
Diarrheal diseases are a leading cause of global morbidity and mortality, disproportionately affecting children in resource-limited settings. Although improvements in hygiene and access to clean water are helpful, vaccines are considered essential due to the low infectious dose of species and increasing antibiotic resistance. Building on achievements with conjugate vaccines, a safe and immunogenic novel bioconjugate vaccine linking O-antigen to Pseudomonas aeruginosa exoprotein A has been developed to induce immunity against Shigella flexneri 2a, 3a, and 6 and S. sonnei. This study evaluated the breadth of reactivity and functionality of pooled serum from rabbits immunized with monovalent and quadrivalent bioconjugates formulated with or without an adjuvant against serotypes isolated in Kenya. Rabbit sera were assayed by colony blot for reactivity with 67 isolates of serotypes targeted by the vaccine, S. flexneri (2a, 3a, and 6) and S. sonnei, and 42 isolates of serotypes not targeted by the vaccine, S. flexneri (1b, 2b, 4a, and 4b), S. boydii, and S. dysenteriae. isolates testing positive in the colony blot assay were then used to assess functional activity using a bactericidal assay. Of the 41 isolates targeted by the vaccine, 22 were reactive with the adjuvanted quadrivalent and the respective monovalent rabbit sera. The S. flexneri 2a and 3a monovalent rabbit serum cross-reacted with S. flexneri 3a, 2b, and 2a, respectively. Immunization with the adjuvanted quadrivalent vaccine also induced cross-reactivity with isolates of S. flexneri 2b, 4a, and 4b. Collectively, these results suggest that the quadrivalent vaccine may be more broadly protective than designed, offering a promising solution to infections. Diarrheal diseases are the third leading cause of death globally, disproportionally affecting low- to middle-income countries like Kenya, with species being the leading cause of bacterial diarrhea, especially in children. The low infectious dose and high antibiotic resistance levels complicate treatment, leading to long-term sequelae that necessitate control measures such as vaccines to reduce morbidity and mortality rates, especially among children under 5 years of age. A quadrivalent bioconjugate vaccine was recently developed to safely and effectively induce immunity against four important spp. This study demonstrates the breadth of reactivity and functionality of the parenterally administered bioconjugate vaccine by evaluating the ability of rabbit sera to bind and kill isolates recently collected in Kenya. These results suggest that the quadrivalent vaccine may be more broadly protective than designed and may offer a promising solution to the morbidity and mortality associated with infections.
腹泻病是全球发病率和死亡率的主要原因，在资源有限的环境中，儿童受其影响尤为严重。尽管改善卫生条件和获得清洁水有助于减少腹泻病的发生，但由于 物种的感染剂量低且抗生素耐药性不断增加，疫苗被认为是必不可少的。在结合疫苗取得成就的基础上，开发了一种新型安全免疫原性生物缀合物疫苗，将 O-抗原与铜绿假单胞菌外蛋白 A 连接，以诱导针对福氏志贺菌 2a、3a 和 6 以及宋内志贺菌的免疫。本研究评估了用单价和四价生物缀合物免疫的兔子血清在肯尼亚分离的血清型针对 67 株 血清型分离株的反应广度和功能，这些血清型是疫苗的目标血清型，福氏志贺菌（2a、3a 和 6）和宋内志贺菌，以及 42 株未针对疫苗目标的血清型分离株，福氏志贺菌（1b、2b、4a 和 4b）、鲍氏志贺菌和痢疾志贺菌。在菌落印迹检测中呈阳性的 分离株随后用于使用杀菌测定评估功能活性。在疫苗针对的 41 株 分离株中，有 22 株与佐剂四价和相应单价兔血清发生反应。福氏志贺菌 2a 和 3a 单价兔血清分别与福氏志贺菌 3a、2b 和 2a 发生交叉反应。用佐剂四价疫苗免疫也诱导了与福氏志贺菌 2b、4a 和 4b 分离株的交叉反应。总的来说，这些结果表明，四价疫苗可能比设计的更具广泛保护性，为 感染提供了一种有希望的解决方案。腹泻病是全球第三大死因，不成比例地影响到肯尼亚等中低收入国家， 物种是细菌性腹泻的主要原因，尤其是在儿童中。感染剂量低和高水平的抗生素耐药性使治疗变得复杂，导致需要控制措施，如疫苗，以降低发病率和死亡率，尤其是 5 岁以下儿童。最近开发了一种四价生物缀合 疫苗，以安全有效地诱导针对四种重要 spp 的免疫。本研究通过评估兔血清结合和杀死最近在肯尼亚收集的 分离株的能力，展示了经皮给予的生物缀合疫苗的反应广度和功能。这些结果表明，四价疫苗可能比设计的更具广泛保护性，为与 感染相关的发病率和死亡率提供了一种有希望的解决方案。
