Inhalational monkeypox virus infection in cynomolgus macaques

Area of Science:

• Virology
• Infectious Diseases
• Animal Models

Background:

• Monkeypox virus (MPXV) poses a significant public health threat.
• Developing reliable animal models is crucial for understanding MPXV pathogenesis and evaluating countermeasures.
• Previous models may not fully recapitulate human inhalation exposure routes.

Purpose of the Study:

• To characterize an aerosol inhalation exposure system for MPXV.
• To develop and validate a non-human primate (NHP) model of MPXV inhalation infection in cynomolgus macaques.
• To determine the lethal dose 50 (LD50) for inhaled MPXV in this model.

Main Methods:

• Characterization of a head-only aerosol exposure system for MPXV.
• Evaluation of liquid impingement (impinger) and impaction (gelatin filter) for aerosol sampling.
• Aerosol particle size determination (MMAD) to ensure alveolar deposition.
• Exposure of cynomolgus macaques to varying doses of aerosolized MPXV.
• Monitoring animal health, survival, and determining the inhalation LD50.

Main Results:

• Both impinger and gelatin filter methods provided comparable MPXV aerosol concentrations.
• Aerosol particle size (MMAD 1.08–1.15 μm) confirmed suitability for alveolar delivery.
• Four out of six macaques succumbed to MPXV infection, with survival in the lowest dose groups.
• The inhalation LD50 was established at approximately 7.8 × 10^4 plaque-forming units (PFU).

Conclusions:

• A robust MPXV inhalation model in cynomolgus macaques has been successfully developed.
• The model demonstrates a disease course and lethal dose comparable to existing literature.
• This NHP model is suitable for studying MPXV pathogenesis and testing interventions via inhalation.