Understanding the biology of monkeypox virus to prevent future outbreaks.

Historically, monkeypox (mpox) was a zoonotic disease endemic in Africa. However, in 2022, a global outbreak occurred following a substantial increase in cases in Africa, coupled with spread by international travellers to other continents. Between January 2022 and October 2023, about 91,000 confirmed cases from 115 countries were reported, leading the World Health Organization to declare a public health emergency. The basic biology of monkeypox virus (MPXV) can be inferred from other poxviruses, such as vaccinia virus, and confirmed by genome sequencing. Here the biology of MPXV is reviewed, together with a discussion of adaptive changes during MPXV evolution and implications for transmission. Studying MPXV biology is important to inform specific host interactions, to aid in ongoing outbreaks and to predict those in the future.

Comparison of the immunogenicity and protective efficacy of ACAM2000, MVA, and vectored subunit vaccines for Mpox in rhesus macaques.

The 2022-2023 mpox outbreak triggered vaccination efforts using smallpox vaccines that were approved for mpox, including modified vaccinia Ankara (MVA; JYNNEOS), which is a safer alternative to live replicating vaccinia virus (ACAM2000). Here, we compare the immunogenicity and protective efficacy of JYNNEOS by the subcutaneous or intradermal routes, ACAM2000 by the percutaneous route, and subunit Ad35 vector-based L1R/B5R or L1R/B5R/A27L/A33R vaccines by the intramuscular route in rhesus macaques. All vaccines provided robust protection against high-dose intravenous mpox virus challenge with the current outbreak strain, with ACAM2000 providing near complete protection and JYNNEOS and Ad35 vaccines providing robust but incomplete protection. Protection correlated with neutralizing antibody responses as well as L1R/M1R- and B5R/B6R-specific binding antibody responses, although additional immune responses likely also contributed to protection. This study demonstrates the protective efficacy of multiple vaccine platforms against mpox virus challenge, including both current clinical vaccines and vectored subunit vaccines.