使用基于重组植物的口服疫苗进行黏膜免疫。

Mucosal immunization using recombinant plant-based oral vaccines.

作者信息

Streatfield Stephen J

机构信息

Applied Biotechnology Institute, 101 Gateway Boulevard, Suite 100, College Station, TX 77845, USA.

出版信息

Methods. 2006 Feb;38(2):150-7. doi: 10.1016/j.ymeth.2005.09.013.

Abstract

The induction of mucosal immunity is very important in conferring protection against pathogens that typically invade via mucosal surfaces. Delivery of a vaccine to a mucosal surface optimizes the induction of mucosal immunity. The apparent linked nature of the mucosal immune system allows delivery to any mucosal surface to potentially induce immunity at others. Oral administration is a very straightforward and inexpensive approach to deliver a vaccine to the mucosal lining of the gut. However, vaccines administered by this route are subject to proteolysis in the gastrointestinal tract. Thus, dose levels for protein subunit vaccines are likely to be very high and the antigen may need to be protected from proteolysis for oral delivery to be efficacious. Expression of candidate vaccine antigens in edible recombinant plant material offers an inexpensive means to deliver large doses of vaccines in encapsulated forms. Certain plant tissues can also stably store antigens for extensive periods of time at ambient temperatures, obviating the need for a cold-chain during vaccine storage and distribution, and so further limiting costs. Antigens can be expressed from transgenes stably incorporated into a host plant's nuclear or plastid genome, or from engineered plant viruses infected into plant tissues. Molecular approaches can serve to boost expression levels and target the expressed protein for appropriate post-translational modification. There is a wide range of options for processing plant tissues to allow for oral delivery of a palatable product. Alternatively, the expressed antigen can be enriched or purified prior to formulation in a tablet or capsule for oral delivery. Fusions to carrier molecules can stabilize the expressed antigen, aid in antigen enrichment or purification strategies, and facilitate delivery to effector sites in the gastrointestinal tract. Many antigens have been expressed in plants. In a few cases, vaccine candidates have entered into early phase clinical trials, and in the case of farmed animal vaccines into relevant animal trials.

摘要

诱导黏膜免疫对于抵御通常通过黏膜表面入侵的病原体至关重要。将疫苗递送至黏膜表面可优化黏膜免疫的诱导。黏膜免疫系统明显的关联特性使得向任何一个黏膜表面给药都有可能在其他黏膜表面诱导免疫。口服给药是将疫苗递送至肠道黏膜的一种非常直接且廉价的方法。然而,通过这种途径给药的疫苗在胃肠道中会受到蛋白水解作用。因此,蛋白质亚单位疫苗的剂量水平可能会非常高,并且为了使口服给药有效,可能需要保护抗原免受蛋白水解。在可食用的重组植物材料中表达候选疫苗抗原提供了一种以包封形式递送大剂量疫苗的廉价手段。某些植物组织还可以在环境温度下长时间稳定储存抗原,从而在疫苗储存和分发过程中无需冷链,进而进一步降低成本。抗原可以从稳定整合到宿主植物核基因组或质体基因组中的转基因表达,也可以从感染到植物组织中的工程化植物病毒表达。分子方法可用于提高表达水平,并将表达的蛋白质靶向进行适当的翻译后修饰。对于处理植物组织以实现可口产品的口服递送,有多种选择。或者,可以在制成口服片剂或胶囊制剂之前富集或纯化表达的抗原。与载体分子融合可以稳定表达的抗原,有助于抗原富集或纯化策略,并促进递送至胃肠道中的效应部位。许多抗原已在植物中表达。在少数情况下,候选疫苗已进入早期临床试验,对于养殖动物疫苗则进入了相关动物试验。

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