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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