Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Vaccine. 2013 Nov 19;31(48):5772-7. doi: 10.1016/j.vaccine.2013.07.064. Epub 2013 Aug 19.
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 rDEN4Δ30. 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.
西尼罗河病毒（WNV）已成为美国主要的虫媒病毒脑炎病原体。尽管大多数 WNV 感染为无症状感染，但约 20%的感染会导致西尼罗河热，1%会导致西尼罗河神经侵袭性疾病（WNND），引起脑炎、脑膜炎或弛缓性瘫痪。老年人患 WNND 的风险特别高，超过一半的病例发生在 60 岁以上的人群中。目前还没有针对 WNND 的许可治疗方法，也没有针对人类预防 WNV 感染的许可疫苗。美国国立卫生研究院传染病实验室已基于嵌合野生型 WNV NY99 基因组与减毒登革热病毒 4 型候选疫苗 rDEN4Δ30 ，开发了一种重组减毒活 WNV 疫苗。DENV-4 的 prM 和包膜蛋白基因被 WNV NY99 的基因取代，由此产生的病毒被命名为 rWN/DEN4Δ30。该疫苗在两项独立研究中，在 18-50 岁的健康黄病毒初免成年志愿者中进行了评估，现将两项研究报告如下。第一项研究评估了单次剂量给予 10³或 10⁴ PFU 的疫苗；第二项研究评估了 10⁵ PFU 的疫苗，两次剂量相隔 6 个月。在所有三种剂量下，疫苗均具有良好的耐受性和免疫原性，单次剂量后，74%（10³PFU）、75%（10⁴PFU）和 55%（10⁵PFU）的受试者血清转化为西尼罗河病毒 NY99。第一次剂量 6 个月后给予第二次 10⁵ PFU 的 rWN/DEN4Δ30 剂量，将血清转化率提高到 89%。基于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估候选疫苗。
