Insights into Monkeypox Virus: Host Immunity, Viral Immune Evasion, Recent Advances in Vaccines, Therapeutic Development, and Future Perspectives

Monkeypox (Mpox), a zoonotic viral disease caused by the Monkeypox Virus (MPXV), has gained significant attention in recent years due to its increasing incidence and the grave threat it poses to global health. MPXV has spread at a rapid pace during the COVID-19 pandemic, causing 10,000+ confirmed cases and ~300 fatalities in 122 countries. This virus comprises two major clades, Clade I (Central African), which is evidently more virulent, and Clade II (West African), which has caused the recent outbreaks across the world and caused fewer deaths. Clinically, Mpox presents as a milder form with fever, lymphadenopathy, and vesiculopustular rash similar to smallpox. Diagnostic measures such as polymerase chain reaction (PCR) are the main diagnostic confirmatory tools. Advanced diagnostics involve electronic microscopy, serology, and immunohistochemistry. Alternative drugs like tecovirimat and brincidofovir have demonstrated potential for treating smallpox, but there is scanty evidence on their efficacy against MPXV. Most recent advancements in the study of vaccines have resulted in the creation and introduction of MVA-BN (JYNNEOS/Imvanex/Imvamune) and ACAM2000 vaccines, which conferred cross-protection against MPXV. MVA-BN is suggested to perform better than other types due to its enhanced safety and immunogenicity. Researchers are also developing DNA and protein subunit vaccines against Mpox to induce specific immune responses by presenting viral proteins. The discovery of novel vaccine candidates and antiviral treatments will be needed to prevent future outbreaks and reduce the global health burden of Mpox. This review focuses on the characterization of MPXV, summarizing current knowledge on its genomic structure, pathogenesis, replication, potential targets of anti-MPXV drugs, clinical features, and epidemiological patterns, along with recent advances in vaccine development.