Sun Haiyan, Acharya Dhiraj, Paul Amber M, Lai Huafang, He Junyun, Bai Fengwei, Chen Qiang
The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Department of Cell and Molecular Biology, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Vaccines (Basel). 2023 Jan 17;11(2):197. doi: 10.3390/vaccines11020197.
West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue (DENV) virus. Specifically, a plant-produced virus-like particle (VLP) that displays the WNV Envelope protein domain III (wDIII) elicited both high neutralizing antibody titers and antigen-specific cellular immune responses in mice. Passive transfer of serum from VLP-vaccinated mice protected recipient mice from a lethal challenge of WNV infection. Notably, VLP-induced antibodies did not enhance the infection of Fc gamma receptor-expressing K562 cells by ZIKV or DENV through ADE. Thus, a plant-made wDIII-displaying VLP presents a promising WNV vaccine candidate that induces protective immunity and minimizes the concern of inducing ADE-prone antibodies to predispose vaccinees to severe infection by DENV or ZIKV.
西尼罗河病毒（WNV）在全球每年都会引发疫情，是美国蚊媒疾病的主要病因。在缺乏获批治疗方法的情况下，迫切需要研发针对WNV的有效且安全的人用疫苗。WNV疫苗研发的主要安全问题之一是，接种疫苗的个体可能会因抗体依赖性增强感染（ADE）而增加感染相关黄病毒的风险。在此，我们报告了一种基于植物的候选疫苗的研发情况，该疫苗可使小鼠在面对致死性WNV攻击时产生保护性免疫，同时将感染寨卡病毒（ZIKV）和登革病毒（DENV）时出现ADE的风险降至最低。具体而言，一种表达WNV包膜蛋白结构域III（wDIII）的植物源病毒样颗粒（VLP）在小鼠体内引发了高中和抗体滴度以及抗原特异性细胞免疫反应。将VLP疫苗接种小鼠的血清被动转移，可保护受体小鼠免受WNV感染的致死性攻击。值得注意的是，VLP诱导产生的抗体不会通过ADE增强ZIKV或DENV对表达Fcγ受体的K562细胞的感染。因此，一种植物制造的展示wDIII的VLP是一种很有前景的WNV候选疫苗，它能诱导保护性免疫，并将诱导易于引发ADE的抗体从而使疫苗接种者易患DENV或ZIKV严重感染的担忧降至最低。
