TO THE EDITOR—We read with interest the article by Ogale et al [1] in which they report on the presence of mpox virus exposure using direct (polymerase chain reaction [PCR]) and serological (anti-orthopox virus immunoglobulin G [IgG] and IgM) methods in patients who present for their first JYNNEOS vaccine administration without characteristic lesions or rash. The authors found that of 324 patients without a positive PCR specimen, 47 (15%) presented with a positive anti-orthopox virus IgG titer, 6 also with a positive IgM titer. Two additional patients presented with IgM positivity only. Considering that 36 of these patients were aged> 50 years or had a known history of smallpox vaccination, we could speculate that in this subsample, 13 of 324 patients (4%) could have been exposed to the mpox virus. At our center (Infectious Diseases Department, Luigi Sacco Hospital, Milan, Italy), we started our mpox vaccine campaign during the same period reported by Ogale et al with a hybrid model (JYNNEOS vaccine, the first 0.5-mL subcutaneous dose [SC] followed by a 0.1-mL intradermal dose [ID] 4 weeks apart) with blood sampling performed at baseline (first dose, SC: T0), week 4 (second dose, ID: T1), and week 12 (T2). Virus-neutralizing antibody titers were estimated using the plaque reduction neutralization test (PRNT) against the mpox virus. Thus, we were able to assess the proportion of patients who presented with a neutralization titer for mpox at the time of the first vaccine and assess the hybrid vaccination-induced humoral immunity over time. Seventy-seven male patients had an available T0 sample, 6 of whom (7.8%) showed a positive PRNT (range, 1: 10–1: 80), age range of 32–49 years, and none reported previous smallpox vaccination or mpox-related signs or symptoms, suggesting a possible previous unrecognized pauci/asymptomatic mpox infection (mpox-exposed; Table 1)[2]. After excluding 5 patients lost to follow-up, the remaining 66 patients (mpox-unexposed) underwent complete sample collection. At T1, the PNRT for mpox-exposed patients ranged from 1: 20 to 1: 320 (Supplementar y Table 1), and for the mpox-unexposed patients, the median PRNT was 1: 20 (1: 20–1: 40). At T2, PNRT for mpoxexposed patients ranged from 1: 40 to 1: 320 (4 of 6 patients> 1: 160), and for the mpox-unexposed patients, the median PRNT was 1: 40 (1: 20–1: 80). When compared with T1, no mpox-exposed patients showed a decline in PRNT at T2, whereas 17 (25.8%) unexposed patients showed a decline.