National Research Council of Canada-Human Health Therapeutics , Ottawa, Ontario K1A 0R6 , Canada +1 613 991 3210 ;
Expert Opin Drug Deliv. 2015 Jun;12(6):993-1008. doi: 10.1517/17425247.2015.1044435. Epub 2015 May 8.
Many human pathogens cause respiratory illness by colonizing and invading the respiratory mucosal surfaces. Preventing infection at local sites via mucosally active vaccines is a promising and rational approach for vaccine development. However, stimulating mucosal immunity is often challenging. Particulate adjuvants that can specifically target mucosal immune cells offer a promising opportunity to stimulate local immunity at the nasal and/or pulmonary mucosal surfaces.
This review analyzes the common causes of respiratory infections, the challenges in the induction of mucosal and systemic responses and current pulmonary and nasal mucosal vaccination strategies. The ability of various particulate adjuvant formulations, including lipid-based particles, polymers and other particulate systems, to be effectively utilized for mucosal vaccine delivery is discussed.
Induction of antibody and cell-mediated mucosal immunity that can effectively combat respiratory pathogens remains a challenge. Particulate delivery systems can be developed to target mucosal immune cells and effectively present antigen to evoke a rapid and long-term local immunity in the respiratory mucosa. In particular, particulate delivery systems offer the versatility of being formulated with multiple adjuvants and antigenic cargo, and can be tailored to effectively prime immune responses across the mucosal barrier. The opportunity for rational design of novel subunit particulate vaccines is emerging.
许多人类病原体通过定植和侵袭呼吸道黏膜表面引起呼吸道疾病。通过黏膜活性疫苗在局部预防感染是一种很有前途和合理的疫苗开发方法。然而，刺激黏膜免疫通常具有挑战性。能够特异性靶向黏膜免疫细胞的颗粒佐剂为刺激鼻和/或肺黏膜表面的局部免疫提供了一个有希望的机会。
本综述分析了呼吸道感染的常见原因、诱导黏膜和全身反应的挑战以及当前的肺部和鼻腔黏膜疫苗接种策略。讨论了各种颗粒佐剂制剂（包括基于脂质的颗粒、聚合物和其他颗粒系统）在黏膜疫苗传递中有效利用的能力。
诱导能够有效抵抗呼吸道病原体的抗体和细胞介导的黏膜免疫仍然是一个挑战。颗粒递送系统可被开发用于靶向黏膜免疫细胞，并有效地呈现抗原，从而在呼吸道黏膜中迅速引发长期的局部免疫。特别是，颗粒递送系统具有与多种佐剂和抗原有效结合的多功能性，并且可以针对黏膜屏障有效地引发免疫反应。新型亚单位颗粒疫苗的合理设计机会正在出现。
