Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice
Daniela Ogonczyk-Makowska, Pauline Brun, Clémence Vacher, Caroline Chupin, Clément Droillard, Julie Carbonneau, Emilie Laurent, Victoria Dulière, Aurélien Traversier, Olivier Terrier, Thomas Julien, Marie Galloux, Stéphane Paul, Jean‐François Eléouët, Julien Fouret, Marie‐Ève Hamelin, Andrés Pizzorno, Guy Boivin, Manuel Rosa‐Calatrava, Julia Dubois
Abstract
Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses. Altogether, our results showed the versatility of the Metavac® platform and suggested that Metavac®-RSV is a promising mucosal bivalent LAV candidate to prevent pneumovirus-induced diseases.