基于亚单位的黏膜疫苗传递系统用于肺部递药——是否可行?
Subunit-based mucosal vaccine delivery systems for pulmonary delivery - Are they feasible?
机构信息
a School of Biomedical Sciences, Faculty of medicine, The University of Queensland , St Lucia , Australia.
出版信息
Drug Dev Ind Pharm. 2019 Jun;45(6):882-894. doi: 10.1080/03639045.2019.1583758. Epub 2019 Mar 1.
Pulmonary infections are the most common cause of death globally. However, the development of mucosal vaccines that provide protective immunity against respiratory pathogens are limited. In contrast to needle-based vaccines, efficient vaccines that are delivered via noninvasive mucosal routes (such as via the lungs and nasal passage) produce both antigen-specific local mucosal IgA and systemic IgG protective antibodies. One major challenge in the development of pulmonary vaccines using subunit antigens however, is the production of optimal immune responses. Subunit vaccines therefore rely upon use of adjuvants to potentiate immune responses. While the lack of suitable mucosal adjuvants has hindered progress in the development of efficient pulmonary vaccines, particle-based systems can provide an alternative approach for the safe and efficient delivery of subunit vaccines. In particular, the rational engineering of particulate vaccines with optimal physicochemical characteristics can produce long-term protective immunity. These protect antigens against enzymatic degradation, target antigen presenting cells and initiate optimal humoral and cellular immunity. This review will discuss our current understanding of pulmonary immunology and developments in fabricating particle characteristics that may evoke potent and durable pulmonary immunity.
肺部感染是全球范围内最常见的死亡原因。然而,能够提供针对呼吸道病原体的保护性免疫的黏膜疫苗的发展受到限制。与基于针的疫苗不同,通过非侵入性黏膜途径(例如通过肺部和鼻腔)递送的高效疫苗会产生针对特定抗原的局部黏膜 IgA 和系统 IgG 保护性抗体。然而,使用亚单位抗原开发肺部疫苗的一个主要挑战是产生最佳的免疫反应。因此,亚单位疫苗依赖于佐剂来增强免疫反应。尽管缺乏合适的黏膜佐剂阻碍了高效肺部疫苗的发展,但基于颗粒的系统可为安全有效地输送亚单位疫苗提供一种替代方法。特别是,通过合理设计具有最佳物理化学特性的颗粒疫苗可以产生长期的保护性免疫。这些可以保护抗原免受酶的降解,靶向抗原呈递细胞,并引发最佳的体液和细胞免疫。本文将讨论我们对肺部免疫学的现有认识,以及在制造可能引起强烈和持久的肺部免疫的颗粒特性方面的进展。