Evaluation of the short- and long-term immunogenicity of a booster dose of MVA-BN

Mpox is a zoonotic disease, identified in 1970, caused by the monkeypox virus (MPXV). It is endemic in Africa and has two clades: I and II. Since May 2022, mpox (clade II) has spread globally through sexual transmission, primarily among men who have sex with men. Since 2023, clade I has been reported to cause more severe disease in Africa and to spread heterosexually in the Central Africa Region and to children with high case-fatality rate (3-5%). This led the WHO to declare a Public Health Emergency of International Concern (PHEIC) on 14 August 2024. The first case of clade I outside Africa, was identified in Sweden on 15 August 2024. The smallpox Modified Vaccinia Ankara (MVA-BN) vaccine has been authorized in the EU since 2022 for the prevention of mpox, intradermally (ID) or subcutaneously (SC). While no randomized control trial could be performed to demonstrate the efficacy of MVA-BN vaccine against mpox, observational studies have estimated vaccine effectiveness from 20.3% to 79.5% in post exposure prophylaxis (PEP) and approximately 80% in preexposure prophylaxis (PrEP) against symptomatic laboratory-confirmed mpox (1). However, immunogenicity studies showed undetectable neutralizing antibodies one year after vaccination (2), while a US observational cohort study found that mpox cases among fully vaccinated individuals occurred at a median of 266 days after vaccination (3). Due to the risk of Mpox clade I importation, the French Public Health Authority (HAS) has recommended a booster dose since August 29th (4). To date, France is the only country to have recommended such dose. It is based on one immunogenicity study showing that a booster dose at 2 years increases the seroconversion rate of neutralizing antibodies from 5.4% to 98.7% 1 month after booster dose in 70 patients (5). However, the HAS also highlighted the need for more evidence on the durability of a booster dose response, the possibility of a booster administered ID and the impact of the initial number of doses (1 or 2). This study could answer crucial questions on the immunogenicity of MVA-BN as a booster dose, in the context of mpox as a PHEIC: the complete immune characterization of the early immune responses, and their duration