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Published on: March 2, 2014
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 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.
Insights
A novel aerosolized peptide effectively blocks measles virus infection in macaques, offering a new strategy for preventing respiratory viral infections in unvaccinated individuals.
Area of Science:
- Virology
- Immunology
- Drug Delivery
Background:
- Measles is a highly contagious airborne viral illness and a significant cause of child mortality.
- Current prevention relies heavily on vaccination, leaving unvaccinated populations vulnerable.
Purpose of the Study:
- To evaluate the efficacy of an aerosolized lipopeptide fusion inhibitor against measles virus (MeV) respiratory infection.
- To establish a proof-of-concept for inhaled peptide delivery as a protective measure against airborne viral diseases.
Main Methods:
- Development and use of a custom mesh nebulizer for efficient aerosolized peptide delivery to the respiratory tract.
- Administration of the peptide to cynomolgus macaques followed by MeV challenge.
- Assessment of viral load (MeV RNA), infected cells, and host immune responses.
Main Results:
- Aerosolized peptide completely prevented MeV infection in treated macaques.
- No MeV RNA, MeV-infected cells, or MeV-specific humoral responses were detected in treated animals.
- The treatment demonstrated an absence of adverse effects and lung pathology.
Conclusions:
- Aerosolized fusion inhibitory peptides provide effective prophylaxis against respiratory measles virus infection.
- This strategy offers a potential new intervention for unvaccinated individuals and can be explored for other airborne viruses like SARS-CoV-2.
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