Immunogenicity and #safety of MVA-BN #vaccine administered 5 years after a two-dose primary series in #DRC: a prospective cohort study

 

Summary

Background

The expanding mpox outbreak in Africa and travel-associated cases in other continents have increased efforts to vaccinate populations at high risk. This study aimed to assess serological immune responses 5 years after individuals received a primary vaccination (two-dose series) with the smallpox and mpox vaccine modified vaccinia Ankara-Bavarian Nordic (MVA-BN), as well as to evaluate the safety and immunogenicity of a third dose (booster). To date, there are no data for immunological memory or third-dose-induced immunity for MVA-BN at these long-term timescales.

Methods

In this open-label, prospective cohort extension, we re-enrolled health-care workers from a 2017 vaccination study in Bokungu Health Zone, DR Congo, to receive a third dose of MVA-BN. All previous participants were offered the opportunity to re-enrol. Participants were grouped according to whether they had received a childhood smallpox vaccination with a replication-competent vaccine strain (historically vaccinated group) or had no history of smallpox vaccination (historically naive group). Participants were excluded from serological analyses if they had any history of mpox or mpox-like lesion-presenting illness, if their previous vaccination status during initial enrolment for the primary series was unknown, or if they had discordant vaccination information. The coprimary outcomes were sustained humoral immunity following primary vaccination with MVA-BN (5 years previously) and the immunogenicity and safety of the booster vaccination. Safety was analysed in patients with a completed immediate adverse event form or adverse event diary. Adverse events were assessed on days 0 (within 30 min of the booster), 7, and 14. Antibody responses were measured by ELISA, plaque reduction neutralisation tests, and endpoint titre at re-enrolment (day 0, before administration of the booster dose) and on days 7, 14, and 545 after the booster dose.

Findings

Between Sept 7 and 15, 2022, 170 (66·1%) of 257 Bokungu health-care personnel vaccinated in 2017 were re-enrolled to receive a third (booster) dose of MVA-BN. At re-enrolment, low levels of circulating antibody were observed, but 30 (61%) of 49 historically naive participants and 95 (96%) of 99 historically vaccinated participants with childhood smallpox vaccination remained seropositive 5 years after the primary MVA-BN two-dose series. After the third dose, there was a rapid and massive increase in anti-orthopoxvirus IgG but not IgM, and a 93-fold rise in orthopoxvirus neutralising antibody titres was observed by day 14 in historically naive participants, irrespective of participants' seropositivity at the time of booster vaccination. The third dose resulted in enhanced durability of circulating antibody concentrations, with endpoint titres on day 545 remaining more than six-fold higher than day 0 values. There was a greater risk of local reactogenicity after the booster dose than after the primary vaccination (relative risk 4·2, 95% CI 2·81–6·46), but there was no difference in the risk of systemic adverse events up to day 7 after vaccination. No grade 3 serious adverse events were recorded after booster dose administration.

Interpretation

These data show that primary MVA-BN vaccination induces sustained immunological memory up to 5 years after vaccination and that a booster dose strongly enhances circulating antibody levels and durability. Future studies should clarify the role of circulating antibody concentrations as a correlate of protection from monkeypox virus infection.

Funding

US Centers for Disease Control and Prevention and US Biomedical Advanced Research and Development Authority.

Translation

For the French translation of the abstract see Supplementary Materials section.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00001-0/fulltext?rss=yes

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