Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination.

Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination.
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DOI:
10.1016/j.celrep.2022.110388
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发表时间:
2022-02-15
期刊:
影响因子:
8.8
通讯作者:
Pinto AK
Pinto AK
中科院分区:
生物学1区
文献类型:
--
作者:
Stone ET;Hassert M;Geerling E;Wagner C;Brien JD;Ebel GD;Hirsch AJ;German C;Smith JL;Pinto AK

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Powassan病毒(POWV)是一种蜱传病原体,人类是其偶然宿主。POWV感染可能是致命的或导致长期的神经系统后遗症;然而,没有批准的POWV疫苗。有效疫苗开发的组成部分是保护相关性的鉴定,我们在本研究中通过利用POWV感染的小鼠模型完成了这一鉴定。使用POWV致死和亚致死攻击模型,我们表明:(1)稳健的B和T细胞应答是免疫保护所必需的,(2)POWV致死性可归因于病毒和宿主介导的疾病驱动因素,以及(3)针对POWV的免疫保护相关性的知识可应用于基于病毒样颗粒(VLP)的疫苗接种方法,该方法提供针对致死POWV攻击的保护。这些免疫保护因子的鉴定是重要的,因为它将有助于POWV疫苗的合理设计。Stone等人描述了在感染的鼠模型中的Powassan病毒(POWV)适应性免疫保护。这种理解在疫苗接种方法中达到高潮,该疫苗接种方法增强针对POWV发病率和死亡率的保护性适应性免疫应答。这些发现将有助于满足未满足的合理设计POWV疫苗的需求。
Powassan virus (POWV) is a tick-borne pathogen for which humans are an incidental host. POWV infection can be fatal or result in long-term neurological sequelae; however, there are no approved vaccinations for POWV. Integral to efficacious vaccine development is the identification of correlates of protection, which we accomplished in this study by utilizing a murine model of POWV infection. Using POWV lethal and sub-lethal challenge models, we show that (1) robust B and T cell responses are necessary for immune protection, (2) POWV lethality can be attributed to both viral- and host-mediated drivers of disease, and (3) knowledge of the immune correlates of protection against POWV can be applied in a virus-like particle (VLP)-based vaccination approach that provides protection from lethal POWV challenge. Identification of these immune protection factors is significant as it will aid in the rational design of POWV vaccines. Stone et al. describe Powassan virus (POWV) adaptive immune protection in a murine model of infection. This understanding culminates in a vaccination approach that elicits protective adaptive immune responses against POWV morbidity and mortality. These findings will aid in fulfilling the unmet need for rational design of POWV vaccinations.
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