The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers.
The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers.
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DOI：
10.1016/j.vaccine.2013.07.064
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发表时间：
2013-11-19
期刊：
影响因子：
5.5
通讯作者：
Pletnev, Alexander G.
中科院分区：
文献类型：
--
作者：
Durbin, Anna P.;Wright, Peter F.;Cox, Amber;Kagucia, Wangeci;Elwood, Daniel;Henderson, Susan;Wanionek, Kimberli;Speicher, Jim;Whitehead, Stephen S.;Pletnev, Alexander G.
西尼罗河病毒已成为美国脑膜脑炎的主要媒介传播原因。虽然大多数西尼罗河病毒感染导致无症状的疾病，但大约20%的感染导致西尼罗河热，1%导致西尼罗河神经侵入性疾病（WNND），导致脑炎，脑膜炎或弛缓性麻痹。老年人特别容易患上WNND，超过一半的病例发生在60岁以上的老年人中。目前还没有获得许可的治疗WNND的方法，也没有任何获得许可的疫苗用于人类预防WNV感染。美国国立卫生研究院传染病实验室已经开发了一种重组减毒活WNV疫苗，该疫苗基于野生型WNV NY 99基因组与减毒活DENV-4候选疫苗rDEN 430基因组的嵌合。将编码DENV-4的prM和包膜蛋白的基因替换为WNV NY 99的基因，并将所得病毒命名为rWN/DEN 4 Δ30。在两项独立的研究中，在18 - 50岁的健康黄病毒初治成人志愿者中对该疫苗进行了评价，这两项研究均在本文中报告。第一项研究评价了103或104 PFU的疫苗单次接种;第二项研究评价了105 PFU的疫苗两次接种，间隔6个月。该疫苗在所有三种剂量下均具有良好的耐受性和免疫原性，在单次给药后，74%（103 PFU）、75%（104 PFU）和55%（105 PFU）的受试者诱导血清转化为WNV NY 99。在第一次剂量后6个月给予第二次105 PFU剂量的rWN/DEN 4 Δ30使血清转化率增加89%。根据这些研究的令人鼓舞的结果，计划在50岁以上的成年人中进一步评价候选疫苗。
WNV has become the leading vector-borne cause of meningoencephalitis in the United States. Although the majority of WNV infections result in asymptomatic illness, approximately 20% of infections result in West Nile fever and 1% in West Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or flaccid paralysis. The elderly are at particular risk for WNND, with more than half the cases occurring in persons older than sixty years of age. There is no licensed treatment for WNND nor is there any licensed vaccine for humans for the prevention of WNV infection. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a recombinant live attenuated WNV vaccine based on chimerization of the wild-type WNV NY99 genome with that of the live attenuated DENV-4 candidate vaccine rDEN430. The genes encoding the prM and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the resultant virus was designated rWN/DEN4Δ30. The vaccine was evaluated in healthy flavivirus-naïve adult volunteers age 18 – 50 years in two separate studies, both of which are reported here. The first study evaluated 103 or 104 PFU of the vaccine given as a single dose; the second study evaluated 105 PFU of the vaccine given as two doses 6 months apart. The vaccine was well-tolerated and immunogenic at all three doses, inducing seroconversion to WNV NY99 in 74% (103 PFU), 75% (104 PFU), and 55% (105 PFU) of subjects after a single dose. A second 105 PFU dose of rWN/DEN4Δ30 given 6 months after the first dose increased the seroconversion rate 89%. Based on the encouraging results from these studies, further evaluation of the candidate vaccine in adults older than 50 years of age is planned.
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