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《狂犬病疫苗》讲稿 17:问题与展望 (附:全文的参考文献)

已有 6701 次阅读 2013-7-9 12:11 |个人分类:狂犬病防治|系统分类:科普集锦|关键词:狂犬病 疫苗 讲稿 问题 展望| 问题, 展望, 讲稿, 狂犬, ∫呙

44.17 问题与展望

 在发达国家,家养动物的狂犬病已得到有效控制,对新的人用狂犬病疫苗的兴趣正在降低。但在狂犬病流行的发展中国家,对防控狂犬病的现代产品的需求是迫切的。

狂犬病疫苗是唯一在暴露后使用仍然非常有效的疫苗,而且实际上在过去和现在都主要用于暴露后预防(PEP)。疫苗在暴露后使用的相对效率较低,在处理严重暴露时还可能出问题,此时常常需要同时接种免疫球蛋白。这些事实说明,必须从狂犬病恶性循环的源头上来解决问题,通过对狗和其它动物进行疫苗接种来构建一个保护屏障,以防止人类患病。对狗实施大规模疫苗接种是预防狂犬病由动物传染给人类最有效的方式。只有优先控制了犬狂犬病,才能显著减少人狂犬病的发病率(Charles et al.,2013)

目前细胞培养疫苗(CCRV)是WHO推荐的全球预防狂犬病最有效的疫苗。几十年的经验已经证明,当代狂犬病疫苗是安全有效的,副作用微乎其微,而且与全球儿童疫苗接种的抗原和时间表可以兼容。

在WHO推荐的PEP治疗方案严格执行的情况下,仅有极少数的死亡病例报道记录在文献中。尽管如此,狂犬病每年仍继续杀死数万人并每年消耗数十亿美元。狂犬病的负担大部分落在那些无法提供适当的PEP处置的贫穷国家的民众身上。同样不幸的是,狂犬病继续扩散到以前无狂犬病的地区。

虽然狂犬病在临床上是可预防的,甚至可以在暴露后进行预防,但是缺乏广泛的知晓教育是人类在被感染的动物咬伤后不寻求适当治疗的主要原因。狂犬病生物制品的价格高,按WHO推荐的PEP治疗方案,必须在较长时间内多次跑很远的路程去接种,这些因素都构成暴露于疯动物的个人寻求治疗的障碍。

在暴露前对特定的高风险(非职业)人群进行预防性接种也是一种可行的选择。现在人们正在研究是否要在狂犬病流行区域对儿童进行常规暴露前免疫接种。

目前的新疫苗开发不仅取决于生产技术和病原体/免疫学知识,也取决于监管当局的管理。疫苗的安全性和效力在引进组织培养疫苗后都有明显提高。需要考虑到当前的更高的纯度标准(特别是新的外来因素,如传染性海绵状脑病)。对细胞培养疫苗中使用的稳定剂,如人血清白蛋白,仍应特别注意,稍有疏忽就可能导致疾病传播的危险。

较新的狂犬病生物制品,如针对狂犬病毒抗原的单克隆抗体,目前正在进行临床试验,或正在进行临床前评估,有望为全球提供廉价的被动免疫制剂。减少剂量、可以在一周内完成的PEP和暴露前预防(PrEP)方案,目前也正在进行评估,可能为降低病人的花费提供一种解决方案。

狂犬病疫苗的许多替代产品正处在实验开发的阶段,新的更安全有效的疫苗,如DNA疫苗、以植物为基础的疫苗及重组病毒载体疫苗,应继续得到更多的注意。在任何情况下,利用遗传工程开发狂犬病疫苗都应该符合国内和国际的生物安全指南。如果不断出现新的狂犬病毒,尤其是在蝙蝠中,则需要有保护范围更宽泛的狂犬病疫苗。例如,含有表达嵌合 G蛋白(chimeric G protein,通过源于不同基因型的 G蛋白的 2个部分融合而成)质粒的DNA疫苗,在小鼠体内诱导产生了更广范围的抗体,可以中和各种狂犬病毒。这些嵌合G蛋白可用于制备狂犬病疫苗。此外,还在小鼠试验中将外源性抗原决定基/抗原插入到狂犬病毒G蛋白,这为制备多价疫苗带来了前景。新疫苗载体和佐剂如何激活内在免疫反应以及用于PEP时如何发挥保护作用,应得到进一步的阐明。

分子生物技术正提供新概念来开发全新的狂犬病疫苗。例如,研发中的新型减毒狂犬病活疫苗在安全性、有效性、稳定性和高产方面都具有明显优势。此类疫苗有可能提供迅速和适当的免疫反应,在处理严重病例时有可能规避对昂贵的免疫球蛋白的需求,能够使PEP和PrEP所需的接种次数减为1次,甚至能发挥一定程度的治疗效果。此类疫苗的推广应用将能显著降低使全部人口都得到保护的成本。

在未来的数十年里,对狂犬病毒抗原引发的人类免疫学反应的机制将会有更深入的理解,将导致更安全、更廉价、更有效的生物制剂的开发。高效的犬用口服疫苗可能会是控制狂犬病的一个巨大进步,是经济欠发达地区控制狂犬病所特别需要的。用于特定野生动物载体的口服疫苗已经对狂犬病动物流行病学产生了作用。但是,通过疫苗接种来控制蝙蝠狂犬病在当前还不太可能。

结语:只有通过引进和实施综合的狂犬病控制策略,包括动物控制方案、对人的暴露后预防(PEP)和暴露前预防(PrEP)、公共教育计划和财政承诺,以及公共卫生专业人员、科研人员、实验室技术员、非营利组织和政府官员的通力合作,狂犬病才能最终得到控制(严家新,2009)。

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