Longitudinal assessment of MPXV-specific IgG avidity in patients with Mpox infection

Abstract

Introduction Monkeypox virus (MPXV) infection induces robust humoral immune responses; however, the kinetics of IgG avidity maturation following natural infection remain poorly characterized. Since IgG avidity reflects antibody affinity maturation over time, its evaluation may provide additional information for the interpretation of MPXV serology and infection staging. This study longitudinally assessed MPXV-specific IgG avidity in patients with confirmed mpox infection up to one year after symptom onset. Methods Serum samples from 16 PCR-confirmed mpox patients (clade IIb) were collected within 30 days from symptom onset (T1) and at 3 (T2), 6 (T3), and 12 (T4) months of follow-up, each comprising 13 samples. Anti-MPXV (clade IIb) IgG titers and avidity indices (AI) were evaluated using an in-house indirect immunofluorescence assay (iIFA) performed with and without 4.5 M urea treatment. Neutralizing antibodies (nAbs) were measured by plaque reduction neutralization test (PRNT 50 ). ROC curve analysis was performed to assess the ability of AI to discriminate early from late infection time points. Results All patients developed detectable anti-MPXV IgG within the first month after symptom onset, followed by a progressive decline in antibody titers over time, with average reductions of 1.5-, 2.9-, and 5.8-fold at T2, T3, and T4, respectively. In contrast, IgG avidity progressively increased during follow-up. Mean AI values increased from 0.132 at T1 to 0.619, 0.653, and 0.689 at T2, T3, and T4, respectively. ROC analysis identified an AI cutoff of 0.25 capable of discriminating samples collected within 30 days from those collected at later time points with high accuracy. An inverse correlation between AI and nAbs titers was observed (Spearman’s r = −0.5131, p < 0.0001), suggesting distinct temporal dynamics between antibody maturation and neutralizing activity. Discussion These findings provide one of the first longitudinal descriptions of IgG avidity maturation following natural MPXV infection and support the potential utility of avidity assessment as a complementary serological parameter for distinguishing recent from past infection. Further studies in larger and more diverse cohorts are needed to validate these observations and better define the clinical applicability of MPXV IgG avidity testing.