TOPLINE:

Modified vaccinia Ankara-Bavarian Nordic vaccine-induced antibody responses declined more rapidly than mpox infection-induced antibody responses, with mean titres dropping below the seropositivity threshold at more than 1 year post-vaccination. Furthermore, people living with HIV faced accelerated antibody decay and had significantly lower odds of maintaining seropositivity post-vaccination.

METHODOLOGY:

• Researchers conducted a prospective multicentre study to compare long-term antibody responses after mpox infection with those after vaccination with the modified vaccinia Ankara-Bavarian Nordic vaccine.
• They enrolled 122 vaccinated participants (median age, 36 years; 100% men; 25% living with HIV) and 13 participants with polymerase chain reaction-confirmed mpox clade 2b infection (median age, 32.5 years; 100% men; 23% living with HIV).
• Blood samples were collected at a median of 22 months post-vaccination and 25 months post-infection.
• Immunoglobulin G (IgG) titres to the vaccinia virus (VACV) B5 antigen were measured using an electrochemiluminescence assay, with receiver operating characteristic curves determining the seropositivity threshold.

TAKEAWAY:

• Anti-VACV-B5 IgG levels were significantly higher in the infection group than in the vaccination group (geometric mean titre, 5092 vs 2958 AU/mL; P < .001); a higher proportion of infected participants remained seropositive at 2 years than vaccinated participants (85% vs 32%; P < .001).
• People living with HIV had 82% lower odds of maintaining seropositivity at 2 years post-vaccination (odds ratio, 0.18; P = .01).
• An anti-VACV-B5 IgG titre of 3284 AU/mL was determined as the optimal seropositivity threshold, with a sensitivity of 98% and a specificity of 84% (area under the curve, 0.955; 95% CI, 0.922-0.987).
• Mean predicted antibody titres fell below the seropositivity threshold at 15.5 months post-vaccination, whereas infection-induced antibody titres did not significantly change over time.

IN PRACTICE:

"The observed decline in vaccine-induced antibody titres over time, particularly in PWH [people with HIV], has potential implications for long-term protection and vaccine policy. Given the ongoing PHEIC [Public Health Emergency of International Concern], the waning of vaccine-induced immunity is concerning and underscores the need for continued research into booster strategies, novel vaccine platforms, and tailored approaches to immunisation in vulnerable populations," the authors wrote.

SOURCE:

This study was led by Joanne Byrne, MD, Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland. It was published online on August 30, 2025, in Open Forum Infectious Diseases.

LIMITATIONS:

The study population was limited to adult men, predominantly Caucasian, with no Black African participants. The small sample size in the infection group limited the precision of modelled estimates for antibody kinetics and for assessing HIV's impact on infection-induced antibody responses. Moreover, smallpox vaccination status was inferred from birth year and region, potentially introducing misclassification.

DISCLOSURES:

This study was supported by a grant from the Health Research Board. Some authors reported receiving honoraria, travel grants, consulting fees, and research grants and serving on advisory boards for various pharmaceutical and healthcare companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.