2019年9月2日，《自然—免疫学》在线发表了英国牛津大学Gavin R. Screaton和Juthathip Mongkolsapaya等研究人员的成果。他们研发出一种保护性寨卡病毒疫苗。

据研究人员介绍，登革病毒（DENV）和寨卡病毒（ZIKV）感染可诱导交叉反应的抗体响应。两个免疫显性表位（前体膜蛋白以及包膜（E）蛋白上的融合环表位）能够被交叉反应抗体识别，不仅中和不良，还可以通过Fcγ受体介导的髓样细胞感染的促进病毒复制和疾病严重程度，这一过程被称为抗体依赖性增强（ADE）。ADE是ZIKV和DENV疫苗的重要关注点，因为诱导不良中和的交叉反应抗体可能会引起个体对自然感染的ADE。

研究人员开发了共价稳定的ZIKV E二聚体的设计和生产，其缺乏前体膜蛋白并且不暴露免疫显性融合环表位。用ZIKV E二聚体免疫小鼠诱导二聚体特异性抗体，其在妊娠期间预防ZIKV攻击。重要的是，ZIKV E二聚体诱导的反应不与DENV交叉反应或引起DENV感染的ADE。

附：英文原文

Title: A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection

Author: Jose Luis Slon-Campos, Wanwisa Dejnirattisai, Brett W. Jagger, Csar Lpez-Camacho, Wiyada Wongwiwat, Lorellin A. Durnell, Emma S. Winkler, Rita E. Chen, Arturo Reyes-Sandoval, Felix A. Rey, Michael S. Diamond, Juthathip Mongkolsapaya, Gavin R. Screaton

Issue&Volume: 2019-09-02

Abstract: Infections with dengue virus (DENV) and Zika virus (ZIKV) can induce cross-reactive antibody responses. Two immunodominant epitopesone to precursor membrane protein and one to the fusion loop epitope on envelope (E) proteinare recognized by cross-reactive antibodies13 that are not only poorly neutralizing, but can also promote increased viral replication and disease severity via Fc receptor-mediated infection of myeloid cellsa process termed antibody-dependent enhancement (ADE)1,4,5. ADE is a significant concern for both ZIKV and DENV vaccines as the induction of poorly neutralizing cross-reactive antibodies may prime an individual for ADE on natural infection. In this report, we describe the design and production of covalently stabilized ZIKV E dimers, which lack precursor membrane protein and do not expose the immunodominant fusion loop epitope. Immunization of mice with ZIKV E dimers induces dimer-specific antibodies, which protect against ZIKV challenge during pregnancy. Importantly, the ZIKV E-dimer-induced response does not cross-react with DENV or induce ADE of DENV infection.

DOI: 10.1038/s41590-019-0477-z

Source:https://www.nature.com/articles/s41590-019-0477-z