Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) & Advanced Materials Bio-Engineering Research Centre (AMBER), Trinity College Dublin, Dublin 2, Ireland.
Adv Drug Deliv Rev. 2015 Aug 30;91:52-69. doi: 10.1016/j.addr.2015.03.007. Epub 2015 Mar 25.
While the majority of human pathogens infect the body through mucosal sites, most licensed vaccines are injectable. In fact the only mucosal vaccine that has been widely used globally for infant and childhood vaccination programs is the oral polio vaccine (OPV) developed by Albert Sabin in the 1950s. While oral vaccines against Cholera, rotavirus and Salmonella typhi have also been licensed, the development of additional non-living oral vaccines against these and other enteric pathogens has been slow and challenging. Mucosal vaccines can elicit protective immunity at the gut mucosa, in part via antigen-specific secretory immunoglobulin A (SIgA). However, despite their advantages over the injectable route, oral vaccines face many hurdles. A key challenge lies in design of delivery strategies that can protect antigens from degradation in the stomach and intestine, incorporate appropriate immune-stimulatory adjuvants and control release at the appropriate gastrointestinal site. A number of systems including micro and nanoparticles, lipid-based strategies and enteric capsules have significant potential either alone or in advanced combined formulations to enhance intestinal immune responses. In this review we will outline the opportunities, challenges and potential delivery solutions to facilitate the development of improved oral vaccines for infectious enteric diseases.
虽然大多数人类病原体通过黏膜部位感染人体，但大多数已许可的疫苗都是注射用的。事实上，唯一一种在全球范围内广泛用于婴儿和儿童疫苗接种计划的黏膜疫苗是由阿尔伯特·萨宾（Albert Sabin）在 20 世纪 50 年代开发的口服脊髓灰质炎疫苗（OPV）。虽然已经许可了针对霍乱、轮状病毒和伤寒沙门氏菌的口服疫苗，但针对这些病原体和其他肠道病原体的其他非活体口服疫苗的开发一直缓慢且具有挑战性。黏膜疫苗可以在肠道黏膜处引发保护性免疫，部分是通过抗原特异性分泌型免疫球蛋白 A（SIgA）。然而，尽管它们优于注射途径，但口服疫苗仍面临许多障碍。一个关键的挑战在于设计能够保护抗原免受胃和肠道降解的输送策略，将适当的免疫刺激性佐剂纳入其中，并在适当的胃肠道部位控制释放。许多系统，包括微纳米颗粒、基于脂质的策略和肠溶性胶囊，无论是单独使用还是在先进的联合制剂中，都具有很大的潜力，以增强肠道免疫反应。在这篇综述中，我们将概述促进开发改良的传染性肠道疾病口服疫苗的机会、挑战和潜在的输送解决方案。
