Antigen recognition and immune response to monkeypox virus infection: implications for Mpox vaccine design - a narrative review.

Monkeypox virus (MPXV) is a DNA virus from the Orthopoxvirus genus, sharing significant genomic similarity with the variola virus that causes smallpox. The cessation of smallpox vaccinations has contributed to recent Mpox outbreaks, with reduced immunity levels, particularly in younger populations born after the vaccine was discontinued. The virus triggers innate and adaptive immune responses, with toll-like receptors (TLRs) playing a key role in recognizing viral components and activating proinflammatory cytokines. However, MPXV evades the immune system by producing proteins that inhibit immune signaling pathways. Natural killer (NK) cells and interferons are crucial for early defense, but MPXV impairs their function. Adaptive immunity involves robust antibody and T-cell responses, similar to smallpox vaccination responses. Various mRNA-based candidate vaccines have demonstrated strong immunogenicity, with preclinical studies confirming their ability to trigger potent B-cell and T-cell responses. However, the genetic changes observed in the current outbreak strains necessitate ongoing surveillance of MPXV mutations and their impact on immunogenic proteins. This review aimed to summarize current insights into antigen recognition and immune responses to MPXV, with a focus on key antigenic proteins relevant to vaccine development.