A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens
A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens
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DOI：
10.1016/j.jconrel.2016.05.001
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发表时间：
2016-07-10
影响因子：
10.8
通讯作者：
Lavelle, Ed C.
中科院分区：
文献类型：
--
作者：
Davitt, Christopher J. H.;McNeela, Edel A.;Lavelle, Ed C.
腹泻感染是发病和死亡的主要原因，产肠毒素大肠杆菌（ETEC）和霍乱给全球造成了重大负担。目前还没有获得许可的ETEC疫苗。由于与口服途径相关的物理化学和免疫学挑战，开发新的非活口服疫苗已被证明是困难的。这需要创新的递送解决方案来保护抗原，控制其释放并建立免疫刺激活性。我们描述了单粒多粒（SmPill (R)）疫苗配方，它结合了肠道聚合物涂层的优点，以防止胃pH值低，分散相控制释放和帮助非极性组分的溶解度，以及佐剂和抗原的优化组合，以促进粘膜免疫。我们用表达过定植因子抗原I (CFA/I) JT-49的全细胞灭活大肠杆菌证明了该系统的有效性。在SmPill (R)中，α -半乳酸神经酰胺被鉴定为一种增强JT-49免疫原性的有效佐剂。与分散相相关的细菌在胃pH值下保留在胶囊内，但在肠pH值下释放。接种优化的SmPill (R)制剂可促进肠黏膜中CFA/ i特异性免疫球蛋白A （IgA）的反应，除了血清IgG和一种可溶解的佐剂是有效的必要条件。(C) 2016 Elsevier B.V.版权所有
Diarrhoeal infections are a major cause of morbidity and mortality with enterotoxigenic Escherichia coli (ETEC) and cholera imposing a significant global burden. There is currently no licensed vaccine for ETEC. Development of new nonliving oral vaccines has proven difficult due to the physicochemical and immunological challenges associated with the oral route. This demands innovative delivery solutions to protect antigens, control their release and build in immune-stimulatory activity. We describe the Single Multiple Pill (R) (SmPill (R)) vaccine formulation which combines the benefits of enteric polymer coating to protect against low gastric pH, a dispersed phase to control release and aid the solubility of non-polar components and an optimized combination of adjuvant and antigen to promote mucosal immunity. We demonstrate the effectiveness of this system with whole cell killed E. coli overexpressing colonization factor antigen I (CFA/I), JT-49. Alpha-galactosylceramide was identified as a potent adjuvant within SmPill (R) that enhanced the immunogenicity of JT-49. The bacteria associated with the dispersed phase were retained within the capsules at gastric pH but released at intestinal pH. Vaccination with an optimized SmPill (R) formulation promoted CFA/I-specific immunoglobulin A (IgA) responses in the intestinal mucosa in addition to serum IgG and a solubilized adjuvant was indispensable for efficacy. (C) 2016 Elsevier B.V. All rights reserved.