基因疫苗微粒系统黏膜免疫的研究进展

微粒系统作为一种基因疫苗的黏膜免疫递送系统,能够增强免疫效果,具有同时诱导系统免疫应答和黏膜免疫应答、产生共同黏膜免疫应答、增加病人的顺应性、降低疫苗推广成本等优点.文章综述微粒系统增强基因疫苗黏膜免疫效果的机制、常见的微粒系统、载体材料以及优化微粒系统的研究进展.     

黏膜免疫佐剂及抗原呈递系统研究现状

经济、稳定、高效的黏膜疫苗是目前疫苗研究的新方向,其中,黏膜免疫佐剂及抗原呈递系统是黏膜疫苗研究的重点之一,安全有效的免疫佐剂及抗原呈递系统可大大提高黏膜免疫的效果.       

黏膜免疫和黏膜疫苗研究进展

黏膜免疫包括各种对不同病原体易感的黏膜表面.此文根据黏膜表面的多样性及其独特的组织环境探索黏膜免疫的基本原理,并基于大动物对感染和疫苗接种的免疫应答的实验研究,为研制诱导黏膜免疫的疫苗提供一些思路.     

黏膜免疫佐剂及抗原呈递系统研究现状

经济、稳定、高效的黏膜疫苗是目前疫苗研究的新方向，其中，黏膜免疫佐剂及抗原呈递系统是黏膜疫苗研究的重点之一，安全有效的免疫佐剂及抗原呈递系统可大大提高黏膜免疫的效果。     

疫苗黏膜输送系统的研究进展

疫苗经黏膜接种是一种简单有效的非侵入性给药方式,可同时诱导系统和黏膜免疫应答,且患者顺应性好,成为近年来疫苗接种的研究热点.以合适的药物输送系统为载体可减少抗原的降解和失活,提高免疫原性,减少接种次数.本文综述了纳米乳、胶束、脂质体、纳米粒、免疫刺激复合物和病毒样粒子等疫苗黏膜输送系统相关技术的研究进展.     

抗病毒药物新型给药系统的研究进展

由病毒引发的疾病严重危害人类健康,疫苗为人类对抗病毒感染的重要手段,包括治疗性和预防性疫苗.抗病毒药物的新型口服给约系统(如微乳与自微乳化制剂、黏附微球和纳米凝胶)可提高药物的生物利用度,减轻不良反应.通过微针介导的透皮免疫和呼吸道黏膜免疫可望提高机体的免疫应答及使用者的顺应性.本文综述了抗病毒药的新型口服给药系统,及通过微针介导的透皮和呼吸道黏膜递送疫苗的研究进展.     

抗原传递系统

许多候选疫苗是高度纯化的.但有时单体抗原的免疫原性很低,而抗原传递系统可以优化这类抗原的提呈.新疫苗越来越多,而把这些疫苗纳入免疫计划的机会有限,免疫注射次数受限制,而联合疫苗可能会导致免疫学和物理化学的不相容性,这些问题亦可由抗原传递系统解决.作者就胃肠外和黏膜传递系统的现状进行了阐述,包括基于脂质的系统如脂质体、免疫刺激复合物和多聚微球体.此外,还对无针皮肤传递器材如喷射注射器、微针和贴片进行了描述.     

抗HIV黏膜免疫评价方法研究进展

黏膜是人类免疫缺陷病毒(human immunodeficiency virus,HIV)侵人机体最主要的途径之一,评价黏膜免疫应答对评价HIV疫苗效果至关重要.用于检测不同动物模型和人体黏膜免疫应答的方法不尽相同,包括黏膜取样方法、样品保存、黏膜标记物种类和检测等方面,因此,建立统一的抗HIV黏膜免疫应答评价系统具有...     

克服免疫屏障的黏膜疫苗递送技术研究进展

传染病对人类的生命健康和社会经济均带来巨大影响,而疫苗被证实仍是防治传染病最有效的措施。大多数感染性病原体通过黏膜表面入侵机体。经黏膜途径免疫的疫苗能够在病原体感染部位触发强大的保护性免疫反应,从根本上防止疾病的传播。生物材料和先进的药物递送技术推动黏膜疫苗进入发展的新时代。尽管如此,研究者对黏膜免疫的了解仍然有限,在黏膜疫苗的开发方面仍存在相当大的科学挑战。对黏膜免疫系统的研究现状和黏膜疫苗递送的最新技术进行综述,以期为感染性疾病相关的黏膜疫苗设计与研发提供参考。     

抗动脉粥样硬化基因疫苗经鼻腔免疫黏膜毒性的初步评价

目的:考察抗动脉粥样硬化基因疫苗经鼻腔接种免疫的黏膜毒性.方法:以壳聚糖为基因载体,制备载基因疫苗的壳聚糖纳米粒.对高脂家兔模型滴鼻免疫6次,28周时取鼻黏膜及肺部组织行组织病理学检查,扫描电镜观察鼻黏膜纤毛的超微结构变化.结果:基因疫苗经鼻腔免疫可以显著诱导抗体,延缓动脉粥样硬化的发展.组织病理学检查表明,鼻黏膜及肺部组织形态正常.黏膜纤毛超微结构的扫描电镜观察表明,鼻黏膜纤毛排列有序,无断裂、脱落、倒伏等异常现象.结论:基因疫苗经鼻腔接种未致黏膜及纤毛损伤,鼻腔给药有潜力发展为一种新的接种途径.     

流感疫苗黏膜佐剂研究进展

当前流感疫苗主要为肌内注射灭活疫苗和滴鼻减毒活疫苗.对于预防呼吸道传播的流感,抗原特异性黏膜免疫应答非常重要.现有资料显示,两种疫苗都存在不可避免的局限性,为解决这个问题,需要对黏膜佐剂流感疫苗进行深入的研究.此文对进入临床试验的流感疫苗黏膜佐剂进行综述.     

呼吸道黏膜免疫及其疫苗设计

呼吸道感染是全球公共健康问题,特别是新型冠状病毒肺炎（coronavirus disease 2019,COVID-19）的大流行给全球带来重大生命健康威胁。接种疫苗是预防这一问题的安全、有效且便捷的方式,而经呼吸道黏膜接种疫苗后能在病原体侵入位点提供独特的免疫保护效果。综述将围绕呼吸道黏膜结构及其免疫学机制和呼吸道黏膜疫苗开发的困难,结合COVID-19疫苗开发带来的启示,介绍如何利用佐剂和递送系统设计出效果理想的呼吸道黏膜疫苗。     

Novel approaches for the induction of T helper 1 (Th1)- or Th2-type mucosal and parenteral immune responses

Mucosal surfaces are constantly challenged by micro-organisms and are protected by an integrated component of the immune system called mucosa-associated lymphoreticular tissue (MALT). The immune responses elicited at the mucosal level are regulated by T-helper (Th) cells and involve secretory IgA (S-IgA) antibodies (Abs) and cytotoxic T-lymphocytes (CTLs). Mucosal immunisation has the advantage over parenteral immunisation, of inducing S-IgA Abs and of conferring protection at both the mucosal and parenteral levels; however, administration of soluble antigens through a mucosal route very seldom results in significant mucosal and systemic immune responses. Therefore, appropriate mucosal adjuvants, recombinant bacterial and viral vectors and delivery systems have been developed to increase the immunogenicity of vaccine antigens and to preferentially induce antigen-specific T-helper (Th)1- or Th2-type responses, which in turn result in polarised effector immune responses. Understanding the mechanisms underlying Th1- and Th2-type developmental pathways and the ability of novel mucosal adjuvants and delivery systems to target the desired Th1- or Th2-type immune response would help to design effective mucosal vaccines, inducing predominant cell-mediated or humoral responses.     

Intranasal formulations: promising strategy to deliver vaccines

Introduction: The emergence of new diseases and the lack of efficient vaccines against numerous nontreatable 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.     

New patents on mucosal delivery of vaccines

Background: Noninvasive mucosal immune responses have been shown to be important in controlling various infections through the mucosal route. Therefore, the appropriate induction of humoral, mucosal and cellular immune response should be elicited after immunization. Objective: The objective of this review is to give an overview of novel strategies and patents for the delivery of vaccines through the mucosal route. Method: Different strategies have been developed and patented to facilitate and enhance the mucosal immunity, including the use of lipid-based delivery systems (i.e., liposomes, virosomes, archaeosomes, chochleated, immune stimulating complexes), entrapment/encapsulation of immunogens into polymeric matrix (poly(lactide-co-glycolide), chitosan, alginates, carbopol, gelatin etc.), admixing of immunogens with mucosal adjuvants (cholera toxin or CT, enterotoxin, lipid A, tetanus toxin or lymphotactin), use of live attenuated bacterial and viral vector encoding antigen of interest and ingestible plant-based mucosal vaccines. Conclusion: Lipid- and polymer-based novel delivery systems have been widely investigated in mucosal vaccine delivery systems. Recent advancement in the molecular technology has also shown great potential of genetic immunization for the delivery of wide range of infectious molecular targets. Effective and selective delivery of vaccines through the mucosal route could provide new therapeutic conduit in the treatment of mucous-associated disease.     

Mucosal vaccine delivery

Vaccine development and vaccination is a major growth area of the pharmaceutical industry. As new vaccine products become available, potential will be given to physicians to provide prophylaxis for diseases that were previously not preventable, or to improve immunisation for some diseases that are currently suboptimally covered. Many factors influence vaccine effectiveness but one of the most important is the route of delivery of the product. Mucosal delivery of vaccines allows primary immunisation at the sites of the body where many of mankind’s mortality- and morbidity-causing diseases are initiated. Effective mucosal immunity is best induced by mucosal delivery of vaccines, due to the specialised and interlinked nature of the mucosal lymphoid tissues. As well as the potential for enhanced immunity, mucosal vaccine delivery is expected to increase patient compliance, make vaccines easier to use and reduce the pain, side-effects and fear of parenteral injection. However, mucosal delivery of vaccines is not straightforward and several strategies have been developed to allow for administration by the oral, nasal, rectal, genito-urinary and even pulmonary routes. These strategies include the use of live attenuated micro-organisms, attenuated toxins, bioadhesive polymers and emulsions, liposomes and proteosomes, biodegradable microparticles and immune stimulatory complexes (ISCOMS) as mucosal vaccine delivery systems/adjuvants. Details of some of the recent advances utilising these systems for mucosal antigen delivery are included in the article with a brief discussion on some of the strengths and weaknesses of the various strategies.     

Recent advances in mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymeric carriers

Importance of the field: The mucosal delivery of vaccines provides the basis for induction of humoral, cellular and mucosal immune responses against infectious diseases. The delivery of antigens to and through mucosal barriers always remains challenging due to adverse physiological conditions (pH and enzymes) and biological barriers created by tight epithelial junctions restricting transportation of macromolecules. Mucoadhesive and biodegradable polymers offer numerous advantages in therapeutic delivery of proteins/antigens particularly through the mucosal route by protecting antigens from degradation, increasing concentration of antigen in the vicinity of mucosal tissue for better absorption, extending their residence time in the body and/or targeting them to sites of antigen uptake. Furthermore, antigen can be delivered more effectively to the antigen presenting cells by anchoring the ligand having affinity on the surface of carrier for the receptors present on the mucosal epithelial cells.

Areas covered in this review: The present review covers various polymeric carriers, which allow the possibility of modification and manipulation of their properties, thereby, enhancing the effectiveness of mucosal vaccines. This article reviews the recent literature and patents in the field of vaccine delivery using mucoadhesive polymeric carriers.

What the reader will gain: The reader will gain insights into various natural polymers, synthetic polymers and ligand derived polymeric carrier systems studied to enhance mucosal immunization.

Take home message: Biodegradable polymeric carriers represent a promising approach for mucosal delivery of vaccine.     

Evaluation of albumin microspheres as oral delivery system for Mycobacterium tuberculosis vaccines

Mucosal immunization has been suggested to be the best option for preventing Mycobacterium tuberculosis infection. The purpose of this study was to develop albumin microspheres containing Mycobacterium tuberculosis antigens and to determine if oral administration of the microspheres can induce antigen-specific mucosal and systemic immune responses. Albumin microspheres containing Mycobacterium tuberculosis dead cells and cell lysate were prepared. The physico-chemical characteristics of the formulations were determined and the microspheres were administered to animal models to evaluate the induction of immune responses to the antigens. The results showed that the particle sizes, zeta potential and dissolution pattern of the microspheres were ideal for oral delivery of vaccines. In vivo studies showed high production of antigen-specific antibody production in serum, nasal, salivary and faecal samples. From the results of the study, it can be concluded that oral administration of Mycobacterium tuberculosis microspheres was successful in inducing antigen-specific systemic and mucosal immune responses.