Zuercher Adrian W
Research Immunology, Berna Biotech Ltd, Bern, Switzerland.
Viral Immunol. 2003;16(3):279-89. doi: 10.1089/088282403322396091.
Most viral infections occur via mucosal surfaces like the respiratory, gastrointestinal, or genital epithelium. The mucosal immune system is an important component of the body's defense against such infections and consequently induction of mucosal, in addition to systemic immunity, might improve vaccine efficacy. Several orally administered vaccines, for example, against poliovirus and gastrointestinal bacterial infections, have been developed and are widely used. In contrast, to date most vaccines against respiratory pathogens are applied parenterally and thus do not induce significant mucosal immunity. For the development of effective mucosal vaccines a more profound understanding of the immune mechanisms operative at mucosal surfaces and of the interplay between different mucosal compartments is needed. Moreover, factors like the dose, form of application, and type of mucosal adjuvants are critical to the induction of effective mucosal immunity. This brief review will focus mainly on the nasal route and will summarize some recent findings concerning the function of the mucosal immune system of the upper respiratory tract. Furthermore, routes of cross-immunization between distinct mucosal compartments and how they might be relevant to vaccine development will be addressed. Finally, I will outline critical factors for the rational design of nasal vaccines and in this context highlight some recent preclinical and clinical developments in the field.
大多数病毒感染通过呼吸道、胃肠道或生殖上皮等黏膜表面发生。黏膜免疫系统是机体抵御此类感染的重要组成部分,因此除了诱导全身免疫外,诱导黏膜免疫可能会提高疫苗效力。例如,已经研发出几种口服疫苗,用于预防脊髓灰质炎病毒和胃肠道细菌感染,并且广泛应用。相比之下,迄今为止,大多数针对呼吸道病原体的疫苗都是通过肠胃外途径给药,因此不会诱导显著的黏膜免疫。为了开发有效的黏膜疫苗,需要更深入地了解在黏膜表面起作用的免疫机制以及不同黏膜区室之间的相互作用。此外,剂量、给药形式和黏膜佐剂类型等因素对于诱导有效的黏膜免疫至关重要。本简要综述将主要聚焦于鼻腔途径,并总结一些关于上呼吸道黏膜免疫系统功能的最新发现。此外,还将探讨不同黏膜区室之间的交叉免疫途径及其与疫苗开发的相关性。最后,我将概述鼻腔疫苗合理设计的关键因素,并在此背景下强调该领域最近的一些临床前和临床进展。