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鼻内制剂:递送疫苗的有前景策略。

Intranasal formulations: promising strategy to deliver vaccines.

作者信息

Riese Peggy, Sakthivel Priya, Trittel Stephanie, Guzmán Carlos A

机构信息

Helmholtz Centre for Infection Research, Department of Vaccinology and Applied Microbiology , Inhoffenstrasse 7, 38124 Braunschweig , Germany.

出版信息

Expert Opin Drug Deliv. 2014 Oct;11(10):1619-34. doi: 10.1517/17425247.2014.931936. Epub 2014 Jun 25.

Abstract

INTRODUCTION

The emergence of new diseases and the lack of efficient vaccines against numerous non-treatable pathogens require the development of novel vaccination strategies. To date, only a few mucosal vaccines have been approved for humans. This was in part due to i) the use of live attenuated vaccines, which are not suitable for certain groups of individuals, ii) safety concerns derived from implementation in humans of some mucosal vaccines, iii) the poor stability, absorption and immunogenicity of antigens delivered by the mucosal route and iv) the limited number of available technologies to overcome the bottlenecks associated with mucosal antigen delivery. Recent advances make feasible the development of efficacious mucosal vaccines with adequate safety profile. Thus, currently intranasal vaccines represent an attractive and valid alternative to conventional vaccines.

AREAS COVERED

The present review is focused on the potentials and limitations of market-approved intranasal vaccines and promising candidates undergoing clinical investigations. Furthermore, emerging strategies to overcome main bottlenecks including efficient breaching of the mucosal barrier and safety concerns by implementation of new adjuvants and delivery systems are discussed.

EXPERT OPINION

The rational design of intranasal vaccines requires an in-depth understanding of the anatomic, physicochemical and barrier properties of the nasal mucosa, as well as the molecular mechanisms governing the activation of the local innate and adaptive immune system. This would provide the critical knowledge to establish effective approaches to deliver vaccine antigens across the mucosal barrier, supporting the stimulation of a long-lasting protective response at both mucosal and systemic levels. Current developments in the area of adjuvants, nanotechnologies and mucosal immunology, together with the identification of surface receptors that can be exploited for cell targeting and manipulating their physiological properties, will become instrumental for developing a new generation of more effective intranasal vaccines.

摘要

引言

新疾病的出现以及针对众多无法治疗的病原体缺乏有效的疫苗,这就需要开发新的疫苗接种策略。迄今为止,仅有少数黏膜疫苗被批准用于人类。部分原因在于:i)使用减毒活疫苗,其不适用于某些特定人群;ii)一些黏膜疫苗在人体应用中产生的安全问题;iii)经黏膜途径递送的抗原稳定性、吸收性和免疫原性较差;iv)可用于克服与黏膜抗原递送相关瓶颈的可用技术数量有限。近期的进展使得开发具有足够安全性的有效黏膜疫苗成为可能。因此,目前鼻内疫苗是传统疫苗的一种有吸引力且有效的替代方案。

涵盖领域

本综述聚焦于已获市场批准的鼻内疫苗的潜力和局限性,以及正在进行临床研究的有前景的候选疫苗。此外,还讨论了包括通过实施新佐剂和递送系统有效突破黏膜屏障以及解决安全问题等克服主要瓶颈的新兴策略。

专家观点

鼻内疫苗的合理设计需要深入了解鼻黏膜的解剖学、物理化学和屏障特性,以及控制局部固有免疫和适应性免疫系统激活的分子机制。这将为建立有效的方法以跨黏膜屏障递送疫苗抗原提供关键知识,从而支持在黏膜和全身水平激发持久的保护性反应。佐剂、纳米技术和黏膜免疫学领域的当前进展,以及可用于细胞靶向和操纵其生理特性的表面受体的鉴定,将有助于开发新一代更有效的鼻内疫苗。

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