Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus in Aedes albopictus.

Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus in Aedes albopictus.
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DOI:
10.1089/vbz.2022.0053
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发表时间:
2022-11
影响因子:
2.1
通讯作者:
Vanlandingham, Dana L.
Vanlandingham, Dana L.
中科院分区:
医学4区
文献类型:
--
作者:
Ayers, Victoria B.;Huang, Yan-Jang S.;Dunlop, James I.;Kohl, Alain;Brennan, Benjamin;Higgs, Stephen;Vanlandingham, Dana L.

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包括缓存谷病毒(CVV)和Oropouche病毒在内的几种正丁型病毒(目:Bunyavirales;科:Peribunyaviridae)的出现或重新出现,需要开发和评估候选减毒活疫苗(LAV)。理想情况下,这些疫苗只需一次免疫就能产生持久的免疫力。由于两个毒力因子NSS和NSM的缺失已被证明可以减弱正丁型病毒、静脉型病毒和奈罗型病毒的毒力表型,因此对病毒基因组的遗传操作被认为是合理设计多个家族的布尼亚病毒候选LAV的有效策略。此外,裂谷热病毒NSS和NSM基因的缺失已被证明可以减少蚊子的传播。本研究比较了缺失NSS和NSM基因的CVV突变体(2delCVV)与亲本野生型CVV(WtCVV)6V633株在胸腔注射白纹伊蚊中的复制能力。与wtCVV在注射蚊子中的强劲复制相比,2delCVV突变体的增殖动力学降低了100多倍。这些结果表明,NSM和NSS基因的缺失是合理设计在蚊子中高度减毒的候选正型病毒LAV的可行方法,因此,对毒力和传播的逆转风险很小。
The emergence or re-emergence of several orthobunyaviruses (order: Bunyavirales; family: Peribunyaviridae), including Cache Valley virus (CVV) and Oropouche virus, warrants the development and evaluation of candidate live-attenuated vaccines (LAVs). Ideally, these vaccines would elicit long-lasting immunity with one single immunization. Since the deletion of two virulence factors, NSs and NSm, has been shown to attenuate the virulence phenotype of orthobunyaviruses, phleboviruses, and nairoviruses, genetic manipulation of the viral genome is considered an effective strategy for the rational design of candidate LAVs for bunyaviruses across multiple families. In addition, the deletion of Rift Valley fever virus NSs and NSm genes has been shown to reduce transmission by mosquitoes. In this study, the ability of a CVV mutant lacking the NSs and NSm genes (2delCVV) to replicate in intrathoracically injected Aedes albopictus was compared with the parental wild-type CVV (wtCVV) 6V633 strain. In contrast to the robust replication of wtCVV in injected mosquitoes, the multiplication kinetics of the 2delCVV mutant was reduced by more than a 100-fold. These results suggest that the deletion of NSm and NSs genes is a feasible approach to rationally design candidate orthobunyavirus LAVs that are highly attenuated in mosquitoes and, therefore, pose little risk of reversion to virulence and transmission.
DOI: 10.1186/s13071-018-3103-2
发表时间: 2018-09-20
影响因子: 3.2
作者:
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