Durability of the Humoral Response to MPXV Infection

Mpox virus (MPXV) re-emerged in endemic countries in recent decades, resulting in large outbreaks in central and western Africa and a worldwide epidemic of clade IIb MPXV starting in 2022. Mpox cases in vaccinated persons, and a few documented reinfections, have raised questions about the durability of MPXV humoral immunity. Longitudinal studies conducted during the clade IIb global outbreak have enriched our understanding of immune responses during and after mpox. This commentary aims to summarize current knowledge about the durability of humoral immunity against MPXV and limitations in the available evidence.

Studies following convalescent individuals show vigorous neutralizing antibody titres that peak within weeks after symptom onset and remain detectable for up to 2 years following acquisition. Binding IgG and IgA antibodies directed against MPXV antigens peak and wane more rapidly. Immunodominant epitopes, such as A35R, elicit robust responses. Older individuals who received historical replicating smallpox vaccines and acquired mpox had higher neutralizing and binding antibody titres than younger people, with no apparent difference in durability of humoral immune markers. In some studies, people living with HIV had less vigorous early antibody responses than people without HIV but without an observed difference in durability.

Long-term protection following mpox involves both humoral and cellular immunity. There is no identified correlate of protection for mpox. The current evidence primarily includes studies of mild to moderate clade IIb infection among cohorts largely comprising men in non-endemic countries. Research involving additional viral clades and cohorts with greater breadth of geography, age, gender, race, ethnicity and severity of disease is needed to more fully explore durability of the MPXV immune response. A more complete understanding of this complex picture would likely inform development of improved vaccines and therapeutics for mpox.