Abstract
Monkeypox virus (MPXV) infection in humans results in clinical symptoms very similar to ordinary smallpox. Aerosol is a route of secondary transmission for monkeypox, and a primary route of smallpox transmission in humans. Therefore, an animal model for aerosol exposure to MPXV is needed to test medical countermeasures. To characterize the pathogenesis in cynomolgus macaques (Macaca fascicularis), groups of macaques were exposed to four different doses of aerosolized MPXV. Blood was collected the day before, and every other day after exposure and assessed for complete blood count (CBC), clinical chemistry analysis, and quantitative PCR. Macaques showed mild anorexia, depression, and fever on day 6 post-exposure. Lymphadenopathy, which differentiates monkeypox from smallpox, was observed in exposed macaques around day 6 post-exposure. CBC and clinical chemistries showed abnormalities similar to human monkeypox cases. Whole blood and throat swab viral loads peaked around day 10, and in survivors, gradually decreased until day 28 post-exposure. Survival was not dose dependent. As such, doses of 4×104 PFU, 1×105 PFU, or 1×106 PFU resulted in lethality for 70% of the animals, whereas a dose of 4×105 PFU resulted in 85% lethality. Overall, cynomolgus macaques exposed to aerosolized MPXV develop a clinical disease that resembles that of human monkeypox. These findings provide a strong foundation for the use of aerosolized MPXV exposure of cynomolgus macaques as an animal model to test medical countermeasures against orthopoxviruses.
Highlights
After a centuries-long battle, humans defeated smallpox and it was declared eradicated in 1980
We present that cynomolgus macaques exposed to aerosolized Monkeypox virus (MPXV) show many characteristics of monkeypox and smallpox in humans and is an appropriate model for orthopoxvirus pathogenesis, vaccine and therapeutic studies
Clinical signs and survival In this study, four groups of cynomolgus macaques were exposed to increasing doses of aerosolized MPXV, with a particle size of 1–3 mm (Table 1)
Summary
After a centuries-long battle, humans defeated smallpox and it was declared eradicated in 1980. Vaccinia-based vaccines, used for worldwide eradication of VARV, are protective against MPXV challenge in animal models and are presumed to protect humans from monkeypox [4,5,6,7,8,9,10,11,12]. The similarity of monkeypox to smallpox, and the growing lack of immunity in the population have caused concerns that these viruses might be used as biological weapons. This has prompted scientists to develop new medical countermeasures against poxviruses. It is important to develop a model of MPXV infection in NHPs, using the most relevant route, in order to fully evaluate pathogenesis as well as the capabilities of vaccines and therapeutics
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