CIRI, Centre International de Recherche en Infectiologie, INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon, 21 Avenue Tony Garnier, 69007, Lyon, France.
DTF-Aerodrug, R&D aerosolltherapy department of DTF medical (Saint Etienne, France), Faculté de médecine, Université de Tours, 37032, Tours, France.
Nat Commun. 2022 Oct 28;13(1):6439. doi: 10.1038/s41467-022-33832-6.
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.
麻疹是最具传染性的空气传播病毒感染病，也是疫苗可预防疾病中导致儿童死亡的主要原因。我们在此表明，源自麻疹病毒（MeV）融合蛋白七肽重复区的脂肽融合抑制剂可在食蟹猴非人灵长类动物模型中阻断呼吸道 MeV 感染。我们使用定制设计的网孔雾化器确保肽高效递送至呼吸道，并证明雾化肽在猕猴中无不良影响和肺部病理学改变。雾化肽可有效预防 MeV 感染，导致治疗动物中完全不存在 MeV RNA、MeV 感染细胞和 MeV 特异性体液反应。该策略为针对未接种疫苗人群的呼吸道感染提供了另一种防治手段，可方便地转化为人体试验。它为雾化递送融合抑制肽以预防麻疹和其他空气传播病毒（包括 SARS-CoV-2）提供了概念验证，以防高风险暴露。
