NOVEL VACCINATION STRATEGIES FOR THE CONTROL OF MUCOSAL INFECTION
NOVEL VACCINATION STRATEGIES FOR THE CONTROL OF MUCOSAL INFECTION
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DOI：
10.1016/0264-410x(93)90003-g
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发表时间：
1993-01-01
期刊：
影响因子：
5.5
通讯作者：
HUSBAND, AJ
中科院分区：
文献类型：
--
作者：
HUSBAND, AJ
肠道疾病仍然是人类和兽医物种死亡和发病的最大原因之一。在控制粘膜疾病的疫苗接种方面一直缺乏成功，因此显然需要新的策略来实现有效的粘膜免疫。本文中描述的基础研究已经解决了与抗原处理和肠中免疫应答的诱导以及效应细胞和分子随后向肠和肠外粘膜下层区域的传播相关的问题。伊加应答的有效诱导依赖于T细胞的帮助，并且需要有组织的肠相关淋巴组织（GALT）内T细胞和B细胞之间的同源相互作用。伊加抗体应答递送至粘膜部位也是T细胞依赖性但抗原驱动的过程。GALT摄取抗原的正常途径是通过上皮表面，但以这种方式通过绒毛上皮细胞呈递的抗原主要产生抑制反应。设计用于克服这种效应的策略包括使用强力佐剂（如霍乱毒素、胞壁酰二肽和佛波酯）、使用免疫原性载体或通过脂质体、微球或基因工程病毒或细菌载体递送。或者，已经探索了通过施用油乳剂中的腹膜内抗原经由血清表面接近GALT的可行性，并且已经开发了适合于商业应用中的IP递送的疫苗制剂（Auspharm（专利申请中））。
Enteric disease remains one of the greatest causes of mortality and morbidity in both human and veterinary species. There has been a remarkable lack of success in vaccination to control mucosal disease and it is therefore apparent that novel strategies are required to achieve effective mucosal immunity. Basic studies described in this paper have addressed problems associated with antigen handling and the induction of an immune response in the intestine, and the subsequent dissemination of effector cells and molecules to intestinal and extra-intestinal submucosal regions. Effective induction of IgA responses is dependent on T-cell help and requires cognate interactions between T cells and B cells within organized gut-associated lymphoid tissue (GALT). The delivery of an IgA antibody response to mucosal sites is also a T cell dependent but antigen driven process. The normal route by which antigen is taken up by GALT is via the epithelial surface but antigen presented in this way via villus epithelial cells generates predominantly a suppressor response. Strategies designed to overcome this effect include the use of powerful adjuvants (such as cholera toxin, muramyldipeptide and phorbol esters), the use of immunogenic carriers, or delivery via liposomes, microspheres or genetically engineered viral or bacterial vectors. Alternatively, the feasibility of accessing GALT via the serosal surface by administration of intraperitoneal antigen in oil emulsion has been explored and a vaccine-formulation (Auspharm (patent pending)) has been developed which is suitable for IP delivery in commercial applications.