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狂犬病疫苗的新进展。

New developments in rabies vaccination.

作者信息

Fisher C R, Schnell M J

出版信息

Rev Sci Tech. 2018 Aug;37(2):657-672. doi: 10.20506/rst.37.2.2831.

DOI:10.20506/rst.37.2.2831
PMID:30747119
Abstract

Current rabies vaccines are safe and, when administered properly, they are highly effective. In addition, they elicit long-lasting immunity, with virus-neutralising antibody titres persisting for years after vaccination. However, current regimens require multiple doses to achieve high neutralising titres and they are costly, which means that it is difficult for developing countries, where rabies deaths are highest, to implement widespread vaccination. New innovations are the only way to reduce rabies disease to acceptable rates. Numerous preclinical and clinical studies are under way, testing novel vaccines, adjuvants and injection methods. Research into the use of live vaccines and alternative vaccine vectors is ongoing, while attempts to develop DNA vaccines have so far failed to match the immunogenicity and neutralising capability of traditional vaccines. The development of molecular adjuvants that induce faster, stronger immune responses with less antigen has yielded exciting preclinical results and appears to edge us closer to a better rabies vaccine. However, steep challenges remain: molecular adjuvants require administration with live vaccines, and differences in species specificity of immune molecules complicate development. Over all, the array of research undertaken over the past decade is impressive and encouraging, but most new vaccines have yet to be tested in clinical trials, and the viability of such experimental vaccines in the global market remains to be seen. Only a vaccine that outperforms currently available vaccines in every area will have a chance at widespread adoption. Nevertheless, the authors are confident that some vaccine candidates will meet these criteria.

摘要

目前的狂犬病疫苗是安全的,并且在正确接种时非常有效。此外,它们能引发持久的免疫力,接种疫苗后病毒中和抗体滴度可维持数年。然而,目前的接种方案需要多剂次才能达到高中和滴度,而且成本高昂,这意味着狂犬病死亡人数最多的发展中国家难以实施广泛接种。新的创新是将狂犬病发病率降低到可接受水平的唯一途径。目前正在进行大量临床前和临床研究,测试新型疫苗、佐剂和注射方法。对活疫苗和替代疫苗载体的使用研究正在进行,而开发DNA疫苗的尝试迄今未能达到传统疫苗的免疫原性和中和能力。开发能以更少抗原诱导更快、更强免疫反应的分子佐剂已在临床前研究中取得了令人兴奋的结果,似乎让我们离更好的狂犬病疫苗更近了一步。然而,严峻的挑战依然存在:分子佐剂需要与活疫苗一起使用,而且免疫分子的物种特异性差异使开发变得复杂。总体而言,过去十年所开展的一系列研究令人印象深刻且鼓舞人心,但大多数新疫苗尚未进行临床试验,此类实验性疫苗在全球市场的可行性仍有待观察。只有在各个方面都优于现有疫苗的疫苗才有机会被广泛采用。尽管如此,作者们相信一些候选疫苗将符合这些标准。

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