疟疾疫苗开发现状:疫苗学作用机制的基本方面、疫苗管线、阶段性免疫反应 "挑战与机遇

Solomon Taddese
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引用次数: 0

摘要

疟疾被认为是由疟原虫属细胞内原生动物感染红血球引起的一种全身性综合症,由受感染和生理兴奋的雌性疟蚊叮咬传播,疟蚊吸食疟原虫的血液,产卵并使其成熟。疫苗接种被认为是解决与疟疾有关的发病率和死亡率的最有效方法之一,其方法针对疟疾生命阶段因子,如红细胞前蛋白(RTSs、ChAd63/MVA、METRAP、PSPZ、PfceITos......)、血液阶段蛋白(EBA175、AMA1、GMZ1、P27A、MSP3、MSP1、RH5)、性阶段蛋白(Pfs25、Pfs48、Pfs230 和多阶段/多表位/抗原组合疫苗(PfCP-2.9 嵌合体(AMA1 和 MSP1-19))。尽管疟疾疫苗试验早在 20 世纪 30 年代就已开始,但目前最先进的前红细胞疫苗 RTS S 疫苗已经上市,并具有良好的安全性(有效率为 30-50%)。将不同类型的佐剂结合到抗原特异性制剂中等新方法提高了特定疫苗及其制剂的效力,为疟疾疫苗研究提供了广泛的机会。频繁和多次感染会逐渐产生抗寄生虫免疫力,从而导致疟疾感染者体内的寄生虫血症非常低或检测不到。对疟原虫的绝育免疫虽然从未完全实现,但会产生高度的免疫反应、低水平的寄生虫血症和无症状的带菌者状态。 对于疟疾疫苗的不成功试验,有许多挑战与后勤(控制和调节途径并发症的高成本效益公共卫生干预)、免疫学(疟原虫抗原在每个生命阶段的多态性、寄生虫的免疫逃避策略......)和技术挑战有关。),以及与疟疾疫苗候选物的失误鉴定、佐剂选择和给药途径有关的技术挑战。尽管疟原虫疫苗试验遇到了一些问题,但据报告,在这一轨道上仍有良好的发展机会
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Status in Malaria Vaccine Development: Basic aspects of Vaccinology mechanism of actions, vaccine pipelines, stage oriented immune response ‘Challenges and Opportunities’
Malaria is considered as a systemic syndrome caused by infection of the red blood cells by intracellular protozoan parasites of the genus Plasmodium and is transmitted by the bite of infected and physiologically excited female anopheline mosquito, which feeds on mamamalian blood to produce and mature its eggs. Vaccination is  believed to be one of the most effective approaches to tackle morbidity and mortality  related  malaria and its approach targets the malaria life stage  factors like the pre-erythrocyticproteins (RTSs, ChAd63/MVA, METRAP, PSPZ, PfceITos…), the blood stage proteins (EBA175, AMA1, GMZ1, P27A, MSP3, MSP1, RH5, sexual stage proteins ( Pfs25, Pfs48, Pfs230 and Multi-stage /multi-epitope/antigen combination vaccines ((PfCP-2. 9 chimeric (AMA1 and MSP1–19)). Even if the vaccine trials against malaria was began early in 1930s, currently the one most advanced pre-erythrocyticvaccine, RTS, S vaccine has been launched with good safety profile ( efficacy of 30-50%). New approaches like combining different types of adjuvants into antigen‐specific formulations improved efficacy of a particular vaccine and its formulations offer a wide spectrum of opportunities in malaria vaccine research. Frequent and multiple infections gradually lead to the development of anti-parasite immunity which results in very low or undetectable parasitemia in malaria-infected individuals. Sterilizing immunity against malarial parasite, though never fully achieved, results in a high degree of immune response, low levels of parasitemia, and an asymptomatic carrier status For unsuccessful trials of malaria vaccine, there are so many challenges that are associated to logistic (high cost-effective public health intervention to control and regulate pathway complicity ), immunologic (polymorphism of the malaria parasite antigens in each life stage, the immune evasion strategy of the parasite… ), and technical challenges related to miss identification of malaria vaccine candidates, selection adjuvants and route of administration. Although there were tackles to malarial vaccine trials, it was reported that there are fine opportunities to proceed on the track
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