| Title: |
Development of nebulized inhalation delivery for fusion-inhibitory lipopeptides to protect non-human primates against Nipah-Bangladesh infection |
| Authors: |
Reynard, Olivier; Iampietro, Mathieu; Dumont, Claire; Le Guellec, Sandrine; Durand, Stephanie; Moroso, Marie; Brisebard, Elise; Dhondt, Kévin; Pélissier, Rodolphe; Mathieu, Cyrille; Cabrera, Maria; Le Pennec, Deborah; Amurri, Lucia; Alabi, Christopher; Cardinaud, Sylvain; Porotto, Matteo; Moscona, Anne; Vecellio, Laurent; Horvat, Branka |
| Contributors: |
Centre International de Recherche en Infectiologie (CIRI); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Université de Tours (UT); DTF-Aerodrug; DTF; Laboratoire P4 - Jean Mérieux Lyon; Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM); Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher); École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Expertise en Anatomie Pathologique (APEX); École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Immunobiologie des infections virales – Immunobiology of Viral Infections CIRI (CIRI-IbIV); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon; NeuroInvasion, TROpisme et encéphalite VIRalE CIRI (CIRI-NITROVIRE); Centre d’Etude des Pathologies Respiratoires Tours (CEPR - U 1100); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); Cornell University Ithaca (CU); Vaccine Research Institute Créteil, France (VRI); Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); Institut Mondor de Recherche Biomédicale (IMRB); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); Columbia University Irving Medical Center (CUIMC); Università degli studi della Campania "Luigi Vanvitelli" = University of the Study of Campania Luigi Vanvitelli |
| Source: |
ISSN: 0166-3542 ; Antiviral Research ; https://cnrs.hal.science/hal-05378918 ; Antiviral Research, 2025, 235, pp.106095. ⟨10.1016/j.antiviral.2025.106095⟩. |
| Publisher Information: |
CCSD; Elsevier Masson |
| Publication Year: |
2025 |
| Collection: |
Université François-Rabelais de Tours: HAL |
| Subject Terms: |
Antivirals; Inhibitory lipopeptides; Nebulization; Nipah virus; Non-human primates; Virus-cell-fusion; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology |
| Description: |
International audience ; Nipah virus (NiV) is a lethal zoonotic paramyxovirus that can be transmitted from person to person through the respiratory route. There are currently no licensed vaccines or therapeutics. A lipopeptide-based fusion inhibitor was developed and previously evaluated for efficacy against the NiV-Malaysia strain. Intraperitoneal administration in hamsters showed superb prophylactic activity and promising efficacy, however the intratracheal delivery mode in non-human primates proved intractable and spurred the development of an aerosolized delivery route that could be clinically applicable. We developed an aerosol delivery system in an artificial respiratory 3D model and optimized the combinations of flow rate and particle size for lung deposition. We characterized the nebulizer device and assessed the safety of lipopeptide nebulization in an African green monkey model that mimics human NiV infection. Three nebulized doses of fusion-inhibitory lipopeptide were administered every 24 h, resulting in peptide deposition across multiple regions of both lungs without causing toxicity or adverse hematological and biochemical effects. In peptide-treated monkeys challenged with a lethal dose of NiV-Bangladesh, animals retained robust levels of T and B-lymphocytes in the blood, infection-induced lethality was significantly delayed, and 2 out of 5 monkeys were protected from NiV infection. The present study establishes the safety and feasibility of the nebulizer delivery method for AGM studies. Future studies will compare delivery methods using next-generation fusion-inhibitory anti-NiV lipopeptides to evaluate the potential role of this aerosol delivery approach in achieving a rapid antiviral response. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39870114; PUBMED: 39870114; PUBMEDCENTRAL: PMC12212376 |
| DOI: |
10.1016/j.antiviral.2025.106095 |
| Availability: |
https://cnrs.hal.science/hal-05378918; https://cnrs.hal.science/hal-05378918v1/document; https://cnrs.hal.science/hal-05378918v1/file/nihms-2082847.pdf; https://doi.org/10.1016/j.antiviral.2025.106095 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D64AD00B |
| Database: |
BASE |