Mpox global health emergency: Insights into the virus, immune responses, and advancements in vaccines PART II: Insights into the advancements in vaccines

Abstract

Mpox is currently a global health emergency. This review (Part II) aims to provide insights into Mpox vaccines and their advancements, offering easily digestible information for healthcare workers and researchers. Current Mpox vaccines are all live-attenuated, previously approved for smallpox, and are classified into non-replicating (Modified Vaccinia Ankara-Bavarian Nordic or MVA-BN) and replicating vaccines (Lister clone16m8 KM Biologic or LC16m8KMB and Acambis2000 or ACAM2000). Replicating vaccines offer long-lasting immunity but are contraindicated for immunocompromised individuals and those with extensive dermatitis. Replicating vaccines are administered as a single dose via epicutaneous scarification, while the non-replicating vaccine is given as two subcutaneous doses. Regulatory approvals in various countries are based on animal challenge studies, with limited effectiveness data available. Only LC16m8 is approved for children in Japan, while the others are approved for individuals aged 18 and older. Clinical trials are currently investigating the efficacy and safety of MVA-BN, particularly in children and for post-exposure prophylaxis (PEP). Novel Mpox vaccines that provide cross-protection against orthopoxviruses are needed, with DNA, subunit, and mRNA platforms under development. MPXV-neutralizing antibody-inducing target antigens for vaccine development include the outer envelope antigens of extracellular enveloped virus (EEV): A35R and B6R, and the inner membrane antigens of intracellular mature virus (IMV): M1R, A29L, H3L, and E8L. Two mRNA vaccines are currently in early clinical stages. Importantly, the COVID-19 pandemic underscored the importance of addressing vaccine disparities and improving global access. Transformative approaches are being explored to overcome this challenge and to enhance access in low- and middle-income countries.