Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection

Olivier Reynard, Claudia Gonzalez, Claire Dumont, Mathieu Iampietro, Marion Ferren, Sandrine Guellec, Lajoie Laurie, Cyrille Mathieu, Gabrielle Carpentier, Georges Roseau, Francesca T. Bovier, Yun Zhu, Deborah Pennec, Jérome Montharu, Amin Addetia, Alexander L. Greninger, Christopher A. Alabi, Elise Brisebard, Anne Moscona, Laurent Vecellio, Matteo Porotto and Branka Horvat ()
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Olivier Reynard: INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon
Claudia Gonzalez: INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon
Claire Dumont: INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon
Mathieu Iampietro: INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon
Marion Ferren: INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon
Sandrine Guellec: Université de Tours
Lajoie Laurie: Université de Tours, Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAe), UMR1282, Infectiologie et santé publique (ISP)
Cyrille Mathieu: INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon
Gabrielle Carpentier: PST-A, Université de Tours
Georges Roseau: PST-A, Université de Tours
Francesca T. Bovier: Columbia University Vagelos College of Physicians and Surgeons
Yun Zhu: Columbia University Vagelos College of Physicians and Surgeons
Deborah Pennec: CEPR U1100, Université de Tours
Jérome Montharu: PST-A, Université de Tours
Amin Addetia: University of Washington Medical Center
Alexander L. Greninger: University of Washington Medical Center
Christopher A. Alabi: Cornell University
Elise Brisebard: UMR703, PAnTher APEX, INRAE/Oniris
Anne Moscona: Columbia University Vagelos College of Physicians and Surgeons
Laurent Vecellio: PST-A, Université de Tours
Matteo Porotto: Columbia University Vagelos College of Physicians and Surgeons
Branka Horvat: INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitor, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, blocks respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We use a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptide to the respiratory tract and demonstrate the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevents MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional means to fight against respiratory infection in non-vaccinated people, that can be readily translated to human trials. It presents a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure.

Date: 2022
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DOI: 10.1038/s41467-022-33832-6

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