A plant-produced vaccine protects mice against lethal West Nile virus infection without enhancing Zika or dengue virus infectivity.
A plant-produced vaccine protects mice against lethal West Nile virus infection without enhancing Zika or dengue virus infectivity.
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DOI：
10.1016/j.vaccine.2018.02.073
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发表时间：
2018-03-27
期刊：
影响因子：
5.5
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Lai H;Paul AM;Sun H;He J;Yang M;Bai F;Chen Q
近年来，西尼罗河病毒（WNV）引起了多起全球性疫情，神经侵袭性疾病的频率增加。尽管经过多年的研究，目前还没有获得许可的治疗方法或疫苗可供人类使用。针对西尼罗河病毒的疫苗开发的主要障碍之一是通过抗体依赖性感染增强（ADE）机制在接种受试者中潜在地增强相关黄病毒的感染。例如，最近发现通过预先暴露于WNV而增强寨卡病毒（ZIKV）感染进一步使WNV疫苗的开发复杂化。西尼罗河病毒的流行和当前候选疫苗的潜在ADE风险要求开发有效和安全的疫苗。我们以前曾报道，结构域III（DIII）的WNV包膜蛋白可以很容易地表达在本塞姆氏烟草叶，纯化到同质性，并促进小鼠抗原特异性抗体反应。在此，我们进一步研究了植物制备的DIII（plant-DIII）在提供针对WNV感染的保护性免疫中的体内效力。此外，我们检查了用植物DIII接种疫苗是否会增加ZIKV和登革病毒（DENV）随后感染的风险。植物DIII疫苗接种诱发抗原特异性细胞免疫应答以及体液应答。DIII特异性抗体是中和性的，中和滴度符合与针对多种黄病毒的疫苗的保护性免疫相关的阈值。此外，被动施用抗植物DIII小鼠血清提供了针对小鼠中WNV感染的致死攻击的完全保护。值得注意的是，植物DIII诱导的抗体不增强表达Fc γ受体的细胞中的ZIKV和DENV感染，解决了WNV疫苗在诱导交叉反应性抗体和使受试者对随后的异源黄病毒感染敏感方面的问题。这项研究提供了诱导保护性免疫的WNV亚单位疫苗的第一份报告，同时避免了对ZIKV和DENV感染具有增强活性的抗体的诱导。
West Nile virus (WNV) has caused multiple global outbreaks with increased frequency of neuroinvasive disease in recent years. Despite many years of research, there are no licensed therapeutics or vaccines available for human use. One of the major impediments of vaccine development against WNV is the potential enhancement of infection by related flaviviruses in vaccinated subjects through the mechanism of antibody-dependent enhancement of infection (ADE). For instance, the recent finding of enhancement of Zika virus (ZIKV) infection by pre-exposure to WNV further complicates the development of WNV vaccines. Epidemics of WNV and the potential risk of ADE by current vaccine candidates demand the development of effective and safe vaccines. We have previously reported that the domain III (DIII) of the WNV envelope protein can be readily expressed in Nicotiana benthamiana leaves, purified to homogeneity, and promote antigen-specific antibody response in mice. Herein, we further investigated the in vivo potency of a plant-made DIII (plant-DIII) in providing protective immunity against WNV infection. Furthermore, we examined if vaccination with plant-DIII would enhance the risk of a subsequent infection by ZIKV and Dengue virus (DENV). Plant-DIII vaccination evoked antigen-specific cellular immune responses as well as humoral responses. DIII-specific antibodies were neutralizing and the neutralization titers met the threshold correlated with protective immunity by vaccines against multiple flaviviruses. Furthermore, passive administration of anti-plant DIII mouse serum provided full protection against a lethal challenge of WNV infection in mice. Notably, plant DIII-induced antibodies did not enhance ZIKV and DENV infection in Fc gamma receptor-expressing cells, addressing the concern of WNV vaccines in inducing cross-reactive antibodies and sensitizing subjects to subsequent infection by heterologous flavivirus. This study provides the first report of a WNV subunit vaccine that induces protective immunity, while circumventing induction of antibodies with enhancing activity for ZIKV and DENV infection.
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影响因子：
64.8
作者：
Larocca, Rafael A.;Abbink, Peter;Peron, Jean Pierre S.;Zanotto, Paolo M. de A.;Iampietro, M. Justin;Badamchi-Zadeh, Alexander;Boyd, Michael;Ng'ang'a, David;Kirilova, Marinela;Nityanandam, Ramya;Mercado, Noe B.;Li, Zhenfeng;Moseley, Edward T.;Bricault, Christine A.;Borducchi, Erica N.;Giglio, Patricia B.;Jetton, David;Neubauer, George;Nkolola, Joseph P.;Maxfield, Lori F.;De La Barrera, Rafael A.;Jarman, Richard G.;Eckels, Kenneth H.;Michael, Nelson L.;Thomas, Stephen J.;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
影响因子：
5.5
作者：
Heinz, Franz X.;Holzmann, Heidemarie;Kundi, Michael
通讯作者：
Kundi, Michael
DOI：
10.1007/978-1-4939-3289-4_4
发表时间：
2016-01-01
期刊：
RECOMBINANT PROTEINS FROM PLANTS: METHODS AND PROTOCOLS, 2ND EDITION
影响因子：
--
作者：
Chen, Qiang;Dent, Matthew;Lai, Huafang
通讯作者：
Lai, Huafang
影响因子：
30.3
作者：
Beltramello M;Williams KL;Simmons CP;Macagno A;Simonelli L;Quyen NT;Sukupolvi-Petty S;Navarro-Sanchez E;Young PR;de Silva AM;Rey FA;Varani L;Whitehead SS;Diamond MS;Harris E;Lanzavecchia A;Sallusto F
通讯作者：
Sallusto F
植物生产的抗登革病毒单克隆抗体表现出较低的抗体依赖性感染活性增强效应
影响因子：
3.8
作者：
Dent, Matthew;Hurtado, Jonathan;Chen, Qiang
通讯作者：
Chen, Qiang