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首页> 外文期刊>Vaccine >Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells
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Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells

机译：灭活的全流感病毒颗粒疫苗有效灌注与病毒RNA摄取到抗原呈递细胞中。

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Current detergent or ether-disrupted split vaccines (SVs) for influenza do not always induce adequate immune responses, especially in young children. This contrasts with the whole virus particle vaccines (WPVs) originally used against influenza that were immunogenic in both adults and children but were replaced by SV in the 1970s due to concerns with reactogenicity. In this study, we re-evaluated the immunogenicity of WPV and SV, prepared from the same batch of purified influenza virus, in cynomolgus macaques and confirmed that WPV is superior to SV in priming potency. In addition, we compared the ability of WPV and SV to induce innate immune responses, including the maturation of dendritic cells (DCs) in vitro. WPV stimulated greater production of inflammatory cytokines and type-I interferon in immune cells from mice and macaques compared to SV. Since these innate responses are likely triggered by the activation of pattern recognition receptors (PRRs) by viral RNA, the quantity and quality of viral RNA in each vaccine were assessed. Although the quantity of viral RNA was similar in the two vaccines, the amount of viral RNA of a length that can be recognized by PRRs was over 100-fold greater in WPV than in SV. More importantly, 1000-fold more viral RNA was delivered to DCs by WPV than by SV when exposed to preparations containing the same amount of HA protein. Furthermore, WPV induced up regulation of the DC maturation marker CD86 on murine DCs, while SV did not. The present results suggest that the activation of antigen-presenting DCs, by PRR-recognizable viral RNA contained in WPV is responsible for the effective priming potency of WPV observed in naive mice and macaques. WPV is thus recommended as an alternative option for seasonal influenza vaccines, especially for children. (c) 2021 Elsevier Ltd. All rights reserved.
机译：目前用于流感的洗涤剂或乙醚裂解疫苗（SVs）并不总能诱导足够的免疫反应，尤其是在幼儿中。这与最初用于对抗流感的全病毒颗粒疫苗（WPV）形成了对比。WPV在成人和儿童中都具有免疫原性，但由于对反应原性的担忧，在20世纪70年代被SV取代。在本研究中，我们重新评估了从同一批纯化流感病毒制备的WPV和SV在食蟹猴体内的免疫原性，并确认WPV在启动效力方面优于SV。此外，我们还比较了WPV和SV诱导先天性免疫反应的能力，包括树突状细胞（DC）的体外成熟。与SV相比，WPV刺激小鼠和猕猴免疫细胞产生更多炎性细胞因子和I型干扰素。由于这些先天性反应可能是由病毒RNA激活模式识别受体（PRR）引发的，因此对每种疫苗中病毒RNA的数量和质量进行了评估。尽管两种疫苗中病毒RNA的数量相似，但在WPV中可被PRRs识别的病毒RNA的数量是SV的100倍以上。更重要的是，当暴露于含有相同量HA蛋白的制剂时，WPV向DC输送的病毒RNA是SV的1000倍。此外，WPV诱导小鼠DC上的DC成熟标记物CD86上调，而SV则没有。目前的结果表明，通过WPV中包含的PRR可识别病毒RNA激活抗原呈递DC，是WPV在幼稚小鼠和猕猴中观察到的有效启动效力的原因。因此，建议将WPV作为季节性流感疫苗的替代方案，尤其是针对儿童的疫苗。（c）2021爱思唯尔有限公司保留所有权利。

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