Kinetics of the humoral and cellular immune response up to 1 year from mpox virus infection.

Objectives: The immunological signature of mpox Clade IIb was described in the early stages of infection. We aimed to characterize the kinetics of both humoral and cellular immune responses against mpox from the onset of symptoms up to one year later.

Methods: Sixty-nine patients with mpox infected with Clade IIb during the 2022 outbreak were included in a longitudinal study. Blood samples were collected during the first 3 weeks and 3-4 (T3-4M), 6-8 (T6-8M), and 12 months (T12M) after infection. Mpox-specific IgM, IgA, IgG, and neutralizing antibodies (nAbs) titres were measured by immunofluorescence assay and 50% plaque reduction neutralization test. Interferon-γ producing specific T-cells to Modified Vaccinia Ankara (MVA) peptides was assessed by ELISpot assay. CD4+ and CD8+ T-cells phenotypic markers (CD38/CD57/PD-1) were performed by flow cytometry.

Results: All the humoral markers were detected as early as 4 days and peaked at week 2 (IgG) or 3 (IgM, IgA, nAbs) from symptoms onset. At T3-4M from onset, the antibody levels decreased, and IgM was detected in only one patient; IgA in 50% (13/26), IgG and nAbs in 92% (24/26) of participants. Further decreases in IgG and nAb mean titres were observed at 6-8M. At T12M, IgM, IgA, IgG, and nAbs were detected in 4 (2/47), 48 (23/47), 93 (44/47) and 78% (37/47) of patients, respectively. MVA-specific T-cell response was detected early in the acute phase of infection, peaked at T3M and are maintained until T12M.

Discussion: These data provide evidence of persistence of humoral and cellular immune response 1 year after natural infection, suggesting the maintenance of adequate immune memory. Further study is needed to assess longer persistence of immunity and the cross-protection against different mpox clades.