Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection

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.

A neutralizing antibody prevents postfusion transition of measles virus fusion protein

“…We hypothesized that mAb 77, like the Nipah mAbs 2B12 and 1H1, inhibits viral entry by binding to prefusion F before it has been activated by H-receptor engagement on the target cell. This mechanism differs from that of HRC peptide mimics, which interact with the F protein only after activation of fusion, when the virus has attached to the cell membrane, but before fusion has been completed ( 83 , 84 ). Unexpectedly, however, our mechanistic assays demonstrated that mAb 77 does not block any initiation of conformational change.…”