Impact of apolipoprotein Ε4 (APOE ε4) on neuroimaging outcomes in cognitively healthy midlife adults: A systematic review.

Mpox, caused by the mpox virus (MPXV), is a zoonotic orthopoxvirus first identified in 1958 among macaque monkeys, with the first human case reported in 1970 [–]. Mpox transmission occurs through contact with lesion exudate, crust material, and mucosal excretions from infected animals or humans [–]. Vertical transmission and fomites are other routes of human-to-human transmission [, , ]. Diagnosed patients are advised to isolate with contact tracing [–]. With unprecedented outbreaks in countries outside previously endemic areas of Africa, the World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern on July 23, 2022 []. The MPXV genome spans approximately 198 kb and is functionally organized into a conserved central region responsible for viral replication and variable terminal regions that regulate host range and virulence []. MPXV exists in two infectious forms: mature virions, which facilitate host-to-host transmission, and extracellular virions, which promote intrahost dissemination and immune evasion []. Contemporary vaccine development has therefore focused on surface antigens expressed on both forms, including A29L and M1R on mature virions and A35R and B6R on extracellular virions []. Among these, M1R has emerged as a key immunologic target, as its omission in preclinical models markedly reduces neutralizing antibody responses and results in higher viral loads []. While antivirals (e.g., tecovirimat) have demonstrated safety and efficacy in previous studies, growing resistance has necessitated additional preventative measures [–, ]. Given antigenic similarities between vaccinia virus and MPXV, smallpox vaccination is regarded as a viable strategy for controlling mpox outbreaks [–, , ]. Historical data collected from 1980 to 1984 indicate that the overall attack rate for unvaccinated contacts (7.2%) was significantly higher than that for vaccinated individuals (0.9%) [–]. Currently, two types of smallpox vaccines are approved for human use in the USA and Europe: second-generation ACAM2000 and third-generation modified vaccinia Ankara-Bavarian Nordic (MVA-BN) () [–, –]. ACAM2000 is a replication-competent vaccinia vaccine derived from the New York City Board of Health strain and was approved by the US Food and Drug Administration (FDA) in 2007 for smallpox prevention only [–]. During the 2022 mpox outbreak, ACAM2000 was made available for mpox prevention under an Expanded Access Investigational New Drug protocol []. MVA-BN is a replication-deficient vaccine that received full US FDA approval in 2019 for the prevention of both smallpox and mpox in adults ≥18 years [, ]. The original license specifies subcutaneous administration (0.5 mL per dose, administered as 2 doses 4 weeks apart) []. During the 2022 mpox outbreak, the US FDA issued an Emergency Use Authorization on August 9, 2022, permitting intradermal administration (0.1 mL per dose) to extend vaccine supply and allowing use in individuals <18 years [, ].