H. 18 Development of a Nebulization Approach of Fusion Inhibitory Lipopeptides to Protect Nonhuman Primates against Lethal Respiratory Nipah Virus Infection
Résumé
Nipah virus (NiV) is a fatal zoonotic paramyxovirus that can be transmitted from person to person by the respiratory route, causing encephalitis and severe respiratory disease with an average fatality rate of 75%. There is currently no approved treatment or vaccine for this serious emerging infection. A lipopeptide-based fusion inhibitor strategy has been developed and previously evaluated for efficacy against NiV in vitro and in vivo in hamster and nonhuman primate (NHP) models using intratracheal administration. For human administration by inhalation, a mesh nebuliser and face mask were developed and evaluated in an African green monkey model that mimics human NiV infection. Three consecutive aerosolized doses of the lipopeptide (4mg/kg/24h) resulted in a uniform distribution of the lipopeptide in the respiratory tract. Nebulisation of the peptide was not associated with any apparent allergic reaction, toxicity or adverse haematological and biochemical effects. Peptide treatment significantly delayed lethality in monkeys following intratracheal NiV challenge. The results support the feasibility of nebulisation of antiviral lipopeptides for emergency response to NiV outbreaks. Aerosol delivery of fusion-inhibiting peptides may be used to protect against NiV and other airborne viruses that use the class 1 fusion mechanism for entry.
Domaines
Virologie| Origine | Fichiers produits par l'(les) auteur(s) |
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