López-Camacho César, De Lorenzo Giuditta, Slon-Campos Jose Luis, Dowall Stuart, Abbink Peter, Larocca Rafael A, Kim Young Chan, Poggianella Monica, Graham Victoria, Findlay-Wilson Stephen, Rayner Emma, Carmichael Jennifer, Dejnirattisai Wanwisa, Boyd Michael, Hewson Roger, Mongkolsapaya Juthathip, Screaton Gavin R, Barouch Dan H, Burrone Oscar R, Patel Arvind H, Reyes-Sandoval Arturo
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7BN, UK.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
Vaccines (Basel). 2020 Jun 16;8(2):307. doi: 10.3390/vaccines8020307.
The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.
黄病毒包膜蛋白结构域III（EDIII）是一种针对登革病毒（DENV）和其他相关黄病毒的有效免疫原。这是否可应用于寨卡病毒（ZIKV）疫苗学仍是一个悬而未决的问题。在此，我们使用了几种以不同方式呈递抗原的疫苗平台，测试了ZIKV-EDIII针对ZIKV感染的效力。我们提供的数据表明，用ZIKV-EDIII作为基于DNA或蛋白质的疫苗接种的小鼠，尽管引发了强烈的抗体反应，但在接受ZIKV攻击后，未能产生完全中和抗体，也无法控制病毒血症。此外，我们表明，在复制缺陷型黑猩猩腺病毒（ChAdOx1-EDIII）中编码的ZIKV-EDIII在接种疫苗的小鼠中引发了抗ZIKV包膜抗体，但在两种生理上不同的小鼠攻击模型中对ZIKV的保护作用也有限。综上所述，我们的数据表明，与其他与ZIKV-EDIII有密切相似性的黄病毒（如登革病毒）的情况相反，这种抗原可能不是诱导针对ZIKV的保护性免疫反应的合适疫苗候选物。
