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Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection

Abstract : Zika virus (ZIKV) infection is a serious public health concern due to its ability to induce neurological defects and its potential for rapid transmission at a global scale. However, no vaccine is currently available to prevent ZIKV infection. Here, we report the development of a yeast-derived subunit protein vaccine for ZIKV. The envelope protein domain III (EDIII) of ZIKV was produced as a secretory protein in the yeast Pichia pastoris. The yeast-derived EDIII could inhibit ZIKV infection in vitro in a dose-dependent manner, suggesting that it had acquired an appropriate conformation to bind to cellular receptors of ZIKV. Immunization with recombinant EDIII protein effectively induced antigen-specific binding antibodies and cellular immune responses. The resulting anti-EDIII sera could efficiently neutralize ZIKV representative strains from both Asian and African lineages. Passive transfer with the anti-EDIII neutralizing sera could confer protection against lethal ZIKV challenge in mice. Importantly, we found that purified anti-EDIII antibodies did not cross-react with closely related dengue virus (DENV) and therefore did not enhance DENV infection. Collectively, our results demonstrate that yeast-produced EDIII is a safe and effective ZIKV vaccine candidate.
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Wei Zhang, Panke Qu, Dapeng Li, Chao Zhang, Qingwei Liu, et al.. Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection. Antiviral Research, Elsevier Masson, 2019, 170, pp.104578. ⟨10.1016/j.antiviral.2019.104578⟩. ⟨pasteur-02332684⟩

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