Cell reports. Medicine · 2024
A vaccine targeting antigen-presenting cells through CD40 induces protective immunity against Nipah disease.
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Pastor Yadira, Reynard Olivier, Iampietro Mathieu, Surenaud Mathieu, Picard Florence, El Jahrani Nora, Lefebvre Cécile, Hammoudi Adele, Dupaty Léa, Brisebard Élise, Reynard Stéphanie, Moureaux Élodie, Moroso Marie, Durand Stéphanie, Gonzalez Claudia, Amurri Lucia, Gallouët Anne-Sophie, Marlin Romain, Baize Sylvain, Chevillard Eve, Raoul Hervé, Hocini Hakim, Centlivre Mireille, Thiébaut Rodolphe, Horvat Branka, Godot Véronique, Lévy Yves, Cardinaud Sylvain
Аннотация
Nipah virus (NiV) has been recently ranked by the World Health Organization as being among the top eight emerging pathogens likely to cause major epidemics, whereas no therapeutics or vaccines have yet been approved. We report a method to deliver immunogenic epitopes from NiV through the targeting of the CD40 receptor of antigen-presenting cells by fusing a selected humanized anti-CD40 monoclonal antibody to the Nipah glycoprotein with conserved NiV fusion and nucleocapsid peptides. In the African green monkey model, CD40.NiV induces specific immunoglobulin A (IgA) and IgG as well as cross-neutralizing responses against circulating NiV strains and Hendra virus and T cell responses. Challenge experiments using a NiV-B strain demonstrate the high protective efficacy of the vaccine, with all vaccinated animals surviving and showing no significant clinical signs or virus replication, suggesting that the CD40.NiV vaccine conferred sterilizing immunity. Overall, results obtained with the CD40.NiV vaccine are highly promising in terms of the breadth and efficacy against NiV.