A humoral dilemma: reassessing monkeypox virus neutralizing antibodies at more than two years from Mpox or MVA-BN vaccination

Background. The persistence of immunological memory after immunization against monkeypox virus (MPXV) is unclear. This study assessed MPXV-specific neutralizing antibodies (nAbs) at > 2 years from mpox or Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination. Methods. Retrospective study including individuals with previous mpox or vaccination with MVA-BN, whose MPXV-specific nAb titers were already assessed at 6 months from either event at our center. Neutralizing titers were determined at > 2 years from mpox or vaccination by plaque reduction neutralization test (positive >= 1:10) as the maximum dilution with reduction of cytopathic effect of 90% and 50% (IC90 and IC50). Groups were compared using chi(2) test, Fisher exact test, or Wilcoxon rank-sum test. Association between titers at > 2 years and individuals characteristics was evaluated with ordinal logistic regression. Results. Overall, 48 individuals with previous mpox and 42 vaccinees were included, all were men. At > 2 years from mpox or vaccination, 22 of 90 (24.44%) and 53 of 90 (58.8%) had positive nAb titers, respectively, at IC90 and IC50. At IC50 previous mpox was associated with positive titers (68.75% vs 47.62%; P = .042), with univariate analysis associating higher titers at 6 months to higher titers at > 2 years (odds ratio [OR] = 6.45; 95% confidence interval [CI], 1.89-22.07; P = .003). In multivariate analysis, historical smallpox vaccination was associated with higher titers at > 2 years (OR = 5.37; 95% CI, 1.31-22.00; P = .020), whilst previous mpox was marginally associated (OR = 2.08; 95% CI, .94-4.62; P = .073). Conclusions. This was a retrospective study including individuals with previous mpox or vaccination with MVA-BN whose MPXV-specific nAb titers were already assessed at 6 months from either event. MPXV-specific nAbs waned at > 2 years from previous infection or vaccination, often becoming undetectable. Higher nAb titers at 6 months (univariate) and prior smallpox vaccination (multivariate) were associated with nAb detection at > 2 years, whilst previous mpox was marginally associated.