A vaccine targeting antigen-presenting cells through CD40 induces protective immunity against Nipah disease

Yadira Pastor 1*, Olivier Reynard 2*, Mathieu Iampietro 2, Mathieu Surenaud 1, Florence Picard 1, Nora El Jahrani 1, Cécile Lefebvre 1, Adele Hammoudi 1, Léa Dupaty 1, Élise Brisebard 3, Stéphanie Reynard 4, Élodie Moureaux 5, Marie Moroso 6, Stéphanie Durand 2, Claudia Gonzalez 2, Lucia Amurri 2, Anne-Sophie Gallouët 7, Romain Marlin 7, Sylvain Baize 4, Eve Chevillard 6, Hervé Raoul 6, Hakim Hocini 1, Mireille Centlivre 1, Rodolphe Thiébaut 8, Branka Horvat 2, Véronique Godot 1, Yves Lévy 9, Sylvain Cardinaud 10

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.