In Vivo Imaging of Influenza Virus Infection in Immunized Mice.
In Vivo Imaging of Influenza Virus Infection in Immunized Mice.
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DOI：
10.1128/mbio.00714-17
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发表时间：
2017-05-30
期刊：
影响因子：
6.4
通讯作者：
Subbarao K
中科院分区：
文献类型：
--
作者：
Czakó R;Vogel L;Lamirande EW;Bock KW;Moore IN;Ellebedy AH;Ahmed R;Mehle A;Subbarao K
免疫接种是季节性流感控制的基石，也是大流行防范战略的重要组成部分。使用生物发光报告病毒，我们展示了应用非侵入性体内成像系统（IVIS）技术来评估候选疫苗和免疫疗法在小鼠流感模型中的临床前疗效。顺序成像显示不同的时空动力学的生物发光组的小鼠被动或主动免疫的各种策略，加速清除的挑战病毒在不同的速度和不同的机制。影像学检查结果与肺部病毒滴度得出的结论一致，值得注意的是，在某些情况下，影像学检查结果比传统疗效终点提供的信息更多。我们的研究结果证明了IVIS作为一种定性方法的可靠性，以支持对小鼠流感候选医学对策的临床前评价。甲型流感病毒仍然是对公共卫生的持续威胁。疫苗接种和免疫治疗是控制流感的有效对策，但必须应对抗原漂移和对抗病毒药物产生耐药性的风险。新型疫苗和候选药物的传统临床前有效性研究可能耗时且昂贵，并且范围固有地受到限制。体内成像方法提供了在动物模型中真实的时间非侵入性地跟踪病毒复制的潜力。在这项研究中，我们证明了生物发光成像跟踪流感病毒在免疫小鼠肺部复制的效用，并确定了可能影响成像结果准确解释的重要因素。我们的研究结果支持IVIS方法的潜力，以加强传统的临床前有效性评价的候选疫苗和人单克隆抗体的预防和治疗流感。
Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS) technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titers in the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support preclinical evaluation of candidate medical countermeasures for influenza in mice. Influenza A viruses remain a persistent threat to public health. Vaccination and immunotherapy are effective countermeasures for the control of influenza but must contend with antigenic drift and the risk of resistance to antivirals. Traditional preclinical efficacy studies for novel vaccine and pharmaceutical candidates can be time-consuming and expensive and are inherently limited in scope. In vivo imaging approaches offer the potential to noninvasively track virus replication in real time in animal models. In this study, we demonstrate the utility of bioluminescent imaging for tracking influenza virus replication in the lungs of immunized mice and also identify important factors that may influence the accurate interpretation of imaging results. Our findings support the potential of IVIS approaches to enhance traditional preclinical efficacy evaluation of candidate vaccines and human monoclonal antibodies for the prevention and treatment of influenza.