Japanese encephalitis virus vaccine candidates generated by chimerization with dengue virus type 4

被引：12
作者：
Gromowski, Gregory D. [1 ]
Firestone, Cai-Yen [1 ]
Hanson, Christopher T. [1 ]
Whitehead, Stephen S. [1 ]
机构：
[1] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
来源：
VACCINE | 2014年 / 32卷 / 25期
基金：
美国国家卫生研究院;
关键词：
Japanese encephalitis virus; Chimeric virus; Live-attenuated vaccine; ANTIBODY-MEDIATED NEUTRALIZATION; PHYLOGENETIC ANALYSIS; CAPSID PROTEIN; CORE PROTEIN; FLAVIVIRUS; IMMUNOGENICITY; CLEAVAGE; CONSTRUCTION; REPLICATION; REQUIREMENT;
D O I：
10.1016/j.vaccine.2014.03.062
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor membrane (prM) and envelope (E) protein structural genes of recombinant dengue virus type 4 (rDEN4) or attenuated vaccine candidate rDEN4 Delta 30 with those of wild-type JEV strain India/78. Mutations were engineered in E, NS3 and NS4B protein genes to improve replication in Vero cells. The chimeric viruses were attenuated in mice and some elicited modest but protective levels of immunity after a single dose. One particular chimeric virus, bearing E protein mutation Q264H, replicated to higher titer in tissue culture and was significantly more immunogenic in mice. The results are compared with live-attenuated JEV vaccine strain SA14-14-2. Published by Elsevier Ltd.
引用
收藏
页码：3010 / 3018
页数：9
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