Differences in pathogenicity among the mpox virus clades: impact on drug discovery and vaccine development

Abstract

Since May 2022, mpox virus (MPXV) has attracted considerable attention due to a multi-country outbreak. Marked differences in epidemiology, transmission, and pathology between the 2022 global mpox outbreak (clade IIb) and classical mpox disease, endemic in Africa (clades I and IIa) have been highlighted. MPXV genome analysis has identified the genomic changes characterizing clade IIb and the drivers of MPXV rapid evolution. Although mpox cases have largely declined, MPXV cryptic transmission and microevolution continues, which may lead to an MPXV of unpredictable pathogenicity. Vaccines and antivirals developed against variola virus, the agent that caused the extinguished plague smallpox, have been used to contain the 2022 mpox outbreak. In this review article, recent findings on MPXV origin and evolution and relevant models able to recapitulate differences in MPXV pathogenicity, which are important for drug and vaccine development, are discussed.

Keywords: APOBEC3-driven evolution; in vivo models of mpox virulence; mpox clade pathogenicity; mpox drug discovery; mpox microevolution; vaccine development.