Abstract
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.
Highlights
The Flavivirus genus includes a broad range of pathogenic viruses, some of which are transmitted by the bite of infected hematophagous arthropods [1]
We previously showed that an antigenic design comprised of the envelope protein domain III (EDIII) domain from all four dengue virus (DENV)
The Domain III (DIII) of the Zika envelope protein is an attractive antigen currently explored as an approach for vaccine development
Summary
The Flavivirus genus includes a broad range of pathogenic viruses, some of which are transmitted by the bite of infected hematophagous arthropods [1]. These viruses, including dengue (DENV), yellow fever (YFV), and West Nile (WNV) among others, are the causal agents of a wide variety of conditions that include mild, severe, and fatal hemorrhagic and neurological diseases [2,3,4]. The capsid (C), pre-membrane (prM), and envelope (E) proteins are structurally required to form a viral particle; while NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5, perform non-structural functions, such as polypeptide post-translational processing and RNA replication. Each copy of the E protein folds into a rod-like structure and is composed of three structural domains—domains I and II (EDIDII)
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