Single and 2-dose vaccinations with MVA-BN(R) induce durable B cell memory responses in healthy volunteers that are comparable to older generation replicating smallpox vaccines

While the MVA-BN vaccine has been proven protective against smallpox and monkeypox, the long-term immunological persistence or booster effect has not been described. In this set of clinical studies, participants who had never been immunized against smallpox were randomized to receive, 4 weeks apart: 2 placebo vaccinations (PBO group, N =181); 1 MVA-BN vaccination followed by placebo(1xMVA group, N =181); or 2 MVA-BN vaccinations (2xMVA group, N = 183). In addition, participants with a history of smallpox vaccination received 1 MVA-BN booster (HSPX+ group, N = 200). The 1xMVA and 2xMVA groups responded with increases in neutralizing antibody (nAb) GMTs at Week 2 (5.1 and 4.8, respectively) that further increased at Week 4 (7.2 and 7.5). Two weeks after the second primary vaccination in the 2xMVA group (at Week 6), nAb GMT peaked (45.6) before stabilizing 2 weeks thereafter (at Week 8) (34.0). In the HSPX+ group, a rapid anamnestic response was observed with a peak nAb GMT at Week 2 (175.1) that was much larger than the peak responses in either of the primary vaccination (1x or 2xMVA) dose groups of smallpox vaccine-naive subjects. Persistence of nAbs relative to baseline was observed at 6 months in all groups (highest in HSPX+), with a return to near baseline nAb levels 2 years later. Subsets of [~]75 participants each, who received primary vaccinations in the 1xMVA and 2xMVA groups, were administered an MVA-BN booster 2 years later. Both booster dose (BD) groups exhibited rapid anamnestic responses with nAb GMTs that peaked 2 weeks post-booster (80.7 and 125.3). These post-booster titers in the 1xMVA and 2xMVA groups were higher than those observed at any timepoint following primary vaccination, were comparable to HSPX+ subjects who had been administered a booster, and remained elevated at 6 months post-booster (25.6 and 49.3). The observed anamnestic responses, in the absence of sustained detectable nAbs, support the presence of durable immunological memory following MVA-BN immunization. No safety concerns were identified, and the most common adverse event following the 2-year MVA-BN booster was injection site erythema in 82.2% of participants. Clinical Trial Registry NumbersNCT00316524 and NCT00686582 HighlightsO_LIMVA-BN booster-induced anamnestic responses support durable immune memory C_LIO_LIOne or two primary MVA-BN vaccinations induce similar durable B cell memory responses C_LIO_LIAnamnestic responses were observed in those immunized with MVA-BN 2 years earlier C_LIO_LINo safety concerns were revealed following a 2-year MVA-BN booster C_LI