Preclinical Models for Monkeypox Virus Infection and Therapeutic Development

Monkeypox virus (MPXV) is an emerging virus and its recently identified Clade IIb has caused the greatest global outbreak of this virus family in history. Spread outside of endemic areas associated with atypical transmission modes and clinical presentation initiated the WHO declaration of a Public Health Emergency of International Concern. This large DNA virus causes significant disease with painful lesions and sometimes death often in vulnerable populations such as the young and immunocompromised. Importantly, the effectiveness of orthopoxvirus vaccines vaccination against the new Clade IIb viruses as well as the effectiveness of the vaccine dose sparing strategies that are currently being used are not known. Here we will investigate experimental Clade IIb vs Clade IIa MPXV infection in laboratory models with the goal of developing of a MPXV preclinical model for use in Canadian vaccine development. This model will then be used to understand the mechanisms of MPXV Clade IIb virus disease. For this work, we have three Aims: 1.) to develop preclinical models of MPXV infection using CAST/EiJ mice and black-tailed prairie dogs; 2.) to determine effective modes of transmission for Cade IIb MPXV viruses; 3.) to evaluate approved and newly developed MPXV vaccines against Clade IIb MPXV. Biological sex will also be investigated due to the sex-distribution of MPXV cases in the current outbreak. For this project, we have brought together experts in emerging virus preclinical model development, orthopoxviruses, and virus sequence analysis. Additionally, VIDO has the institutional infrastructure to work with high containment viruses and non-traditional animal models to ensure our success. Together, this project will provide an essential research tool for Canadian scientists and vaccine developers. As well, the results will be important for guiding public health policies to control the outbreak.