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Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection
Olivier Reynard1, Claudia Gonzalez1, Claire Dumont1
1CIRI, 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.
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 inhibitors, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, block respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We used a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptides to the respiratory tract and demonstrated the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevented 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 shield which complements vaccination to fight against respiratory infection, presenting 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, that can be readily translated to human trials.
Insights
Aerosolized fusion inhibitors effectively blocked measles virus infection in macaques, offering a new way to combat this contagious respiratory illness. This approach complements vaccination and may protect against other airborne viruses like SARS-CoV-2.
Area of Science:
- Virology
- Immunology
- Drug Delivery
Background:
- Measles virus (MeV) is a highly contagious airborne pathogen and a primary cause of vaccine-preventable child mortality.
- Existing measles prevention relies heavily on vaccination, necessitating complementary strategies for high-risk exposures.
Approach:
- Developed aerosolized lipopeptide fusion inhibitors targeting the MeV fusion protein's heptad-repeat regions.
- Utilized a custom mesh nebulizer for efficient delivery to the respiratory tract in cynomolgus macaques.
- Assessed safety by monitoring for adverse effects and lung pathology.
Key Points:
- Aerosolized fusion inhibitors completely prevented MeV respiratory infection in a non-human primate model.
- Treated animals showed no detectable MeV RNA, infected cells, or MeV-specific antibody responses.
- The treatment strategy demonstrated no adverse effects or lung pathology.
Conclusions:
- Aerosol delivery of fusion inhibitory peptides is a viable strategy to prevent measles infection.
- This approach offers an additional protective layer complementing measles vaccination.
- The proof-of-concept is applicable to other airborne viruses, including SARS-CoV-2, for post-exposure prophylaxis.
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