Ertl Hildegund C J
The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
PLoS Negl Trop Dis. 2009 Sep 29;3(9):e515. doi: 10.1371/journal.pntd.0000515.
Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP). In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG) preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered.
狂犬病是所有传染病中最致命的一种,在发展中国家仍然是一个重大的公共卫生问题,每年估计有55000人丧生。大多数致命的狂犬病病例是由狗咬伤所致,其中一半以上是儿童,且多发生在东南亚和非洲的低收入家庭。有安全有效的疫苗可用于预防狂犬病。然而,这些疫苗必须多次接种,暴露前接种需三次,暴露后预防(PEP)需四至五次。在严重暴露的情况下,需要采用疫苗与狂犬病免疫球蛋白(RIG)制剂联合使用的方案。致命狂犬病的高发病率与以下因素有关:对咬伤伤口的适当处理缺乏认识、难以获得昂贵的PEP以及未能进行重复免疫接种的后续跟进。需要新型、免疫原性更强但成本更低的狂犬病病毒疫苗,以减少狂犬病对人类生命的威胁。一种用于儿童免疫的预防性疫苗,尤其是在高发病率国家的儿童,有望降低死亡率。这种疫苗必须价格低廉、安全,并能提供持续保护,最好是单剂量接种后即可。还需要新型的PEP方案,以减少对已经稀缺且昂贵的RIG的需求,并将疫苗接种次数减少到一至两次。在这篇综述中,提供了处于临床前测试阶段的新型狂犬病疫苗的研发情况,并对那些可能最适合作为当前使用疫苗潜在替代品的疫苗发表了看法。