Suppression of flavivirus transmission from animal hosts to mosquitoes with a mosquito-delivered vaccine.

Suppression of flavivirus transmission from animal hosts to mosquitoes with a mosquito-delivered vaccine.
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用蚊子传播的疫苗抑制黄病毒从动物宿主传播给蚊子

DOI:
10.1038/s41467-022-35407-x
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发表时间:
2022-12-16
影响因子:
16.6
通讯作者:
Zheng, Aihua
Zheng, Aihua
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wen, Dan;Ding, Limin S.;Zhang, Yanan;Li, Xiaoye;Zhang, Xing;Yuan, Fei;Zhao, Tongbiao;Zheng, Aihua

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人畜共患病病毒在自然水库中传播,并零星地蔓延到人类群体中,导致地方病或大流行。我们先前发现,朝阳病毒是一种昆虫特有的黄病毒,在脊椎动物细胞中是复制缺陷的。在这里,我们开发了一种概念验证蚊子递送疫苗,以环状病毒为载体,在难以接触的野生动物宿主中控制寨卡病毒(ZIKV)。该疫苗是通过用ZIKV的前膜和膜蛋白(PRME)替换ZIKV的蛋白构建而成的,命名为CYV-ZIKV。CyV-ZIKV在伊蚊体内有效复制并传播到唾液,没有观察到性传播或经卵巢传播。为了降低CYV-ZIKV泄漏到环境中的风险,对蚊子进行X射线照射,以确保100%不育,这不会影响唾液中的CYV-ZIKV滴度。通过携带ZIKV的蚊虫叮咬免疫小鼠,可激发强大而持久的ZIKV特异性免疫反应,并对ZIKV攻击提供完全保护。相应地,免疫的小鼠不再能将挑战的ZIKV传播给幼稚的蚊子。因此,通过蚊虫叮咬接种ISF载体疫苗在野生动物宿主中诱导群体免疫是可行的。我们的研究为开发蚊媒疫苗提供了一条未来的途径,以消除森林循环中的人畜共患病病毒。基于先前的研究,即朝阳病毒是一种昆虫特有的黄病毒,只能在昆虫和昆虫细胞中复制,作者提出了这种概念验证蚊媒疫苗;他们构建了一种可通过蚊子叮咬传播的寨卡病毒候选病毒,并评估了其在小鼠身上的免疫应答和保护作用。
Zoonotic viruses circulate in the natural reservoir and sporadically spill over into human populations, resulting in endemics or pandemics. We previously found that the Chaoyang virus (CYV), an insect-specific flavivirus (ISF), is replication-defective in vertebrate cells. Here, we develope a proof-of-concept mosquito-delivered vaccine to control the Zika virus (ZIKV) within inaccessible wildlife hosts using CYV as the vector. The vaccine is constructed by replacing the pre-membrane and envelope (prME) proteins of CYV with those of ZIKV, assigned as CYV-ZIKV. CYV-ZIKV replicates efficiently in Aedes mosquitoes and disseminates to the saliva, with no venereal or transovarial transmission observed. To reduce the risk of CYV-ZIKV leaking into the environment, mosquitoes are X-ray irradiated to ensure 100% infertility, which does not affect the titer of CYV-ZIKV in the saliva. Immunization of mice via CYV-ZIKV-carrying mosquito bites elicites robust and persistent ZIKV-specific immune responses and confers complete protection against ZIKV challenge. Correspondingly, the immunized mice could no longer transmit the challenged ZIKV to naïve mosquitoes. Therefore, immunization with an ISF-vectored vaccine via mosquito bites is feasible to induce herd immunity in wildlife hosts of ZIKV. Our study provides a future avenue for developing a mosquito-delivered vaccine to eliminate zoonotic viruses in the sylvatic cycle. Based on previous research that the Chaoyang virus is an insect-specific flavivirus, only able to replicate in insects and insect cells, authors present this proof-of-concept mosquito-delivered vaccine; they construct a Zika virus focused candidate that can be delivered by mosquito bite, and assess the immune response and protection in mice.
释放不兼容的男性在澳大利亚的野生和沃尔巴契亚岛伊德斯埃及埃及埃及的人群中进行了强烈的抑制。
DOI: 10.1073/pnas.2106828118
发表时间: 2021-10-12
影响因子: 11.1
作者:
Beebe NW;Pagendam D;Trewin BJ;Boomer A;Bradford M;Ford A;Liddington C;Bondarenco A;De Barro PJ;Gilchrist J;Paton C;Staunton KM;Johnson B;Maynard AJ;Devine GJ;Hugo LE;Rasic G;Cook H;Massaro P;Snoad N;Crawford JE;White BJ;Xi Z;Ritchie SA
通讯作者: Ritchie SA
DOI: 10.1371/journal.pntd.0003864
发表时间: 2015
影响因子: 3.8
作者:
Carvalho DO;McKemey AR;Garziera L;Lacroix R;Donnelly CA;Alphey L;Malavasi A;Capurro ML
通讯作者: Capurro ML
DOI: 10.1038/nbt.2019
发表时间: 2011-11-01
影响因子: 46.9
作者:
Harris, Angela F.;Nimmo, Derric;Alphey, Luke
通讯作者: Alphey, Luke
DOI: 10.1016/j.chom.2010.08.007
发表时间: 2010-09-16
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
DOI: 10.4269/ajtmh.17-0126
发表时间: 2017-01-01
影响因子: 3.3
作者:
Eastwood, Gillian;Sang, Rosemary C.;Weaver, Scott C.
通讯作者: Weaver, Scott C.