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疟疾疫苗

Malaria vaccine.

作者信息

Khurana S K, Talib V H

机构信息

Department of Laboratory Medicine, Safdarjang Hospital, New Delhi.

出版信息

Indian J Pathol Microbiol. 1996 Dec;39(5):433-41.

PMID:9002371
Abstract

Recently it has become evident that he same candidate antigen can be shared by several of the parasite stages, and thus the concept of a multistage vaccine is becoming more and more attractive. A TDR Task Force evaluated the promise and stage of development of some 20 existing asexual blood stage candidate antigens and prepared a strategy for their development leading to clinical testing and field trials, Amongst these are merozoite surface protein 1 (MSP-1), Serine Rich Antigen (SERA), Apical Membrane Antigen (AMA-1), and Erythrocyte Binding Antigen (EBA). A field study conducted in Tanzanian children showed that the SPf66 Colombian vaccine was safe, induced antibodies, and reduced the risk of developing clinical malaria by around 30%. This study, confirmed the potential of the vaccine to confer partial protection in areas of high as well as low intensity of transmission. Pfs25 is a leading candidate antigen for a transmission blocking vaccine. It is found in the ookinete stage of the parasite in the mosquito midgut. Gramme amounts of GMP-grade material have been produced and a vaccine based on the Pfs25 antigen formulated with alum should have gone into phase I and II clinical trials in the USA and Africa during 1995. Because the first malaria prototype vaccine to be tried out in people on a large scale has been the polymerized synthetic peptide developed by patarroye on the basis of the SPf66 antigen of P. faliciparum, the results are with much interest. It is still premature to predict the effectiveness of this vaccine globally, but its development will encourage further progress in a fields that has repeatedly been characterized by raised and then dashed drops. These various vaccines are based on the classical approach to vaccination, which is to raise host immunity against the parasite so as to reduce parasite densities or to sterilize an infection. A newer approach is development of antidisease vaccines which aim to alleviate morbidity by suppressing immunopathology in the host. Antidisease vaccines are based on neutralizing parasite components that induce host pathology, leaving the parasite itself directly unaffected. These effects would occur when each type of the disease is considered by it self; however, synergistic effects may be expected when they are used in combination. The rational for vaccines based on any of these stages was that immunization of various hosts with whole parasites of each of these stages has been able to induce protection or total transmission-blocking immunity. Less significant but not to be discounted is the fact that natural malaria infections in humans have been shown to induce immunity against every one of these parasite stages against which vaccines are being developed, an exception to this are those stages that are present only in the mosquito vector with component molecules not presented to the human host, such as exclusively ookinete antigens. For several very apparent reasons a vaccine today is conceived of as subnit as opposed to show1 parasite vaccines, either in the form of a recombinant product or as synthetic peptide constructs. Genes coding for several antigens of P. falciparum and some of P. vivax have been seems to be common to many Plasmodium antigens; this is that they contain tandem repeats of oligopeptide sequences which often code for immunodominant epitopes. Following several decades of research on malaria vaccine development, the field at a glace may present a conflicting picture, with several achievements, and some disappointments and controversies. Issues facing the development of a malaria vaccine are complex. It is not clear how far we may yet be from achieving this goal. The work of the past decades has laid an extensive foundation of ralevant knowledge and technologies, and the goal it self remains as important as ever, will scientists remain committed to this objective?

摘要

最近已经很明显,几种寄生虫阶段可能共享相同的候选抗原,因此多阶段疫苗的概念正变得越来越有吸引力。一个热带病研究培训特别规划署(TDR)特别工作组评估了约20种现有的无性血液阶段候选抗原的前景和开发阶段,并制定了将其开发至临床试验和现场试验的策略。其中包括裂殖子表面蛋白1(MSP-1)、富含丝氨酸抗原(SERA)、顶端膜抗原(AMA-1)和红细胞结合抗原(EBA)。在坦桑尼亚儿童中进行的一项现场研究表明,SPf66哥伦比亚疫苗是安全的,可诱导抗体,并将患临床疟疾的风险降低了约30%。这项研究证实了该疫苗在高传播强度和低传播强度地区提供部分保护的潜力。Pfs25是传播阻断疫苗的主要候选抗原。它存在于蚊子中肠内寄生虫的动合子阶段。已经生产出克级的GMP级材料,一种基于Pfs25抗原并与明矾配制的疫苗本应在1995年在美国和非洲进入I期和II期临床试验。由于首个在人体上大规模试验的疟疾原型疫苗是帕塔罗耶基于恶性疟原虫的SPf66抗原开发的聚合合成肽,其结果备受关注。在全球范围内预测这种疫苗的有效性仍为时过早,但其开发将鼓励在一个反复经历希望燃起又破灭的领域取得进一步进展。这些各种疫苗基于经典的疫苗接种方法,即增强宿主对寄生虫的免疫力,以降低寄生虫密度或消除感染。一种较新的方法是开发抗疾病疫苗,其旨在通过抑制宿主体内的免疫病理学来减轻发病率。抗疾病疫苗基于中和诱导宿主病理的寄生虫成分,而使寄生虫本身直接不受影响。当分别考虑每种疾病类型时会出现这些效果;然而,当它们联合使用时可能会产生协同效应。基于这些阶段中任何一个阶段的疫苗的理论依据是,用这些阶段中每个阶段的完整寄生虫对各种宿主进行免疫接种能够诱导保护或完全的传播阻断免疫。不太显著但也不容忽视的事实是,人类的自然疟疾感染已被证明能诱导针对正在开发疫苗的这些寄生虫阶段中每一个阶段的免疫力,但仅存在于蚊子媒介中且其成分分子不会呈现给人类宿主的那些阶段除外,例如仅动合子抗原。出于几个非常明显的原因,如今疫苗被设想为亚单位疫苗而非全寄生虫疫苗,其形式可以是重组产品或合成肽构建体。编码恶性疟原虫几种抗原以及间日疟原虫一些抗原的基因似乎在许多疟原虫抗原中很常见;这是因为它们包含寡肽序列的串联重复,这些序列通常编码免疫显性表位。经过几十年对疟疾疫苗开发的研究,乍一看该领域可能呈现出一幅矛盾的图景,有一些成就,也有一些失望和争议。疟疾疫苗开发面临的问题很复杂。目前尚不清楚我们距离实现这一目标还有多远。过去几十年的工作奠定了广泛的相关知识和技术基础,而目标本身仍然一如既往地重要,科学家们会继续致力于这一目标吗?

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