Antibody-Based Antigen Delivery to Dendritic Cells as a Vaccination Strategy Against Ebola Virus Disease

Catherine Olal, Bianca S Bodmer, Monika Rottstegge, Beatriz Escudero-Pérez, Julia R Port, András Bencsik, Emily V Nelson, Michelle Heung, Stephanie Wurr, Olivia Blake, Elisa Adam, Lisa Oestereich, Maite Baz-Martínez, Jürgen Müller-Guhl, Yann Gallais, Fabienne Anjuère, Bernard Malliere, Juliana Idoyaga, Thomas Hoenen, César Muñoz-Fontela
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Abstract

Dendritic cells connect innate and adaptive immune responses. This is a particularly important immune checkpoint in the case of emerging infections against which most of the population does not have preexisting antibody immunity. In this study, we sought to test whether antibody-based delivery of Ebola virus (EBOV) antigens to dendritic cells could be used as a vaccination strategy against Ebola virus disease. Our approach was to use antibodies targeting the endocytic receptor DEC-205 present in murine and human dendritic cells, to deliver the EBOV nucleoprotein or the model antigen ovalbumin (OVA). Our findings indicate that DEC-205 targeting stimulated antigen-specific T-cell responses in mice, which resulted in protection from EBOV or recombinant EBOV-OVA challenge. An added value of this strategy was the generation of resident memory T cells. We propose that dendritic cell targeting could be used to improve T-cell responses against filoviruses, a strategy that may complement current vaccination strategies.
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基于抗体的树突状细胞抗原递送作为对抗埃博拉病毒病的疫苗策略
树突状细胞连接先天免疫反应和适应性免疫反应。这是一个特别重要的免疫检查点,在新发感染的情况下,大多数人没有预先存在的抗体免疫。在这项研究中,我们试图测试基于抗体的埃博拉病毒(EBOV)抗原递送到树突状细胞是否可以用作对抗埃博拉病毒病的疫苗接种策略。我们的方法是使用针对小鼠和人树突状细胞中存在的内吞受体DEC-205的抗体来递送EBOV核蛋白或模型抗原卵清蛋白(OVA)。我们的研究结果表明,DEC-205靶向刺激小鼠抗原特异性t细胞反应,从而保护小鼠免受EBOV或重组EBOV- ova的攻击。这种策略的一个附加价值是产生常驻记忆T细胞。我们提出树突状细胞靶向可以用来改善t细胞对丝状病毒的反应,这一策略可以补充当前的疫苗接种策略。
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