Japanese encephalitis vaccine-facilitated dengue virus infection-enhancement antibody in adults.
Japanese encephalitis vaccine-facilitated dengue virus infection-enhancement antibody in adults.
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DOI：
10.1186/s12879-016-1873-8
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发表时间：
2016-10-18
影响因子：
3.7
通讯作者：
Takasaki T
中科院分区：
文献类型：
--
作者：
Saito Y;Moi ML;Takeshita N;Lim CK;Shiba H;Hosono K;Saijo M;Kurane I;Takasaki T
登革病毒（DENV）和日本脑炎病毒（JEV）属于黄病毒属，并且感染该属内的病毒诱导与其他黄病毒交叉反应的抗体。特别是在DENV感染中，针对DENV的抗体具有两种竞争性活性：中和活性和感染增强活性。这些抗体活性被认为是调节DENV感染的临床结果的核心。在这里，我们确定了中和和感染增强活性的DENV交叉反应抗体在成人之前和之后的乙脑疫苗接种。参与者是77名日本成年人，他们接受了单剂量的灭活Vero细胞衍生的乙脑疫苗。在单剂乙脑疫苗接种前或接种后约一个月，共采集了154份血清样本。使用幼仓鼠肾（BHK）细胞和表达Fcγ R的BHK细胞，测定各血清样本对4种DENV血清型的抗体依赖性增强（ADE）活性以及对DENV和JEV的中和活性。在抗DENV IgG ELISA中，总共18个乙脑免疫后样品表现出与DENV的交叉反应性。本研究接种乙脑疫苗后未检测到DENV中和抗体。然而，来自26名参与者的未稀释的乙脑疫苗接种后血清样品对DENV表现出单型和异型ADE活性。在35名乙脑疫苗接种者（35/77，45%）的1：10稀释样本中也观察到ADE活性。总之，乙脑疫苗接种诱导了DENV交叉反应性抗体，并且在亚中和水平下，这些DENV交叉反应性抗体具有DENV感染增强活性。结果还表明，与DENV的交叉反应性与高水平的JEV中和抗体相关，并且通过JE疫苗接种进一步促进DENV交叉反应性。本文的在线版本（doi：10.1186/s12879-016-1873-8）包含补充材料，可供授权用户使用。
Dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the genus Flavivirus, and infection with a virus within this genus induces antibodies that are cross-reactive to other flaviviruses. Particularly in DENV infection, antibodies to DENV possess two competing activities: neutralizing activity and infection-enhancing activity. These antibody activities are considered central in modulating clinical outcomes of DENV infection. Here, we determined the neutralizing and infection-enhancing activity of DENV cross-reactive antibodies in adults before and after JE vaccination. Participants were 77 Japanese adults who had received a single dose of inactivated Vero cell-derived JE vaccine. A total of 154 serum samples were obtained either before or approximately a month after a single dose of JE vaccination. The antibody-dependent enhancement (ADE) activity to each of four DENV serotypes and the neutralizing activities to DENV and to JEV were determined in each of the serum samples by using baby hamster kidney (BHK) cells and FcγR-expressing BHK cells. A total of 18 post-JE immunization samples demonstrated cross-reactivity to DENV in an anti-DENV IgG ELISA. DENV neutralizing antibodies were not detected after JE vaccination in this study. However, undiluted post-JE vaccination serum samples from 26 participants demonstrated monotypic and heterotypic ADE activity to DENV. ADE activity was also observed in 1:10-diluted samples from 35 of the JE vaccine recipients (35/77, 45 %). In summary, JE vaccination induced DENV cross-reactive antibodies, and at sub-neutralizing levels, these DENV cross-reactive antibodies possess DENV infection-enhancement activity. The results also indicate that cross-reactivity to DENV is associated with high levels of JEV neutralizing antibodies and, the DENV cross-reactivity is further facilitated by JE vaccination. The online version of this article (doi:10.1186/s12879-016-1873-8) contains supplementary material, which is available to authorized users.