Single and 2-dose vaccinations with modified vaccinia Ankara-Bavarian Nordic® induce durable B cell memory responses comparable to replicating smallpox vaccines.

BACKGROUND: Though Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN®). vaccination is approved for smallpox and monkeypox prevention, immunological persistence and booster effects remain undescribed.

METHODS: Participants naïve to smallpox vaccination were randomized to 1 dose MVA-BN (1×MVA, N = 181), 2 doses MVA-BN (2×MVA, N = 183), or placebo (N = 181). Participants with previous smallpox vaccination received 1 MVA-BN booster (HSPX+, N = 200). Subsets of the formerly naïve groups (∼75 each) received an MVA-BN booster 2 years later.

RESULTS: Neutralizing antibody (nAb) geometric mean titers (GMTs) increased from 1.1 (baseline, both naïve groups) to 7.2 and 7.5 (Week 4, 1×MVA and 2×MVA, respectively), and further to 45.6 (Week 6, 2×MVA after second vaccination). In HSPX+, nAb GMT rapidly increased from 21.6 (baseline) to 175.1 (Week 2). At 2 years, GMTs for 1×MVA, 2×MVA, and HSPX+ were 1.1, 1.3, and 10.3, respectively. After boosting in the previously naïve groups, nAb GMTs increased rapidly in 2 weeks to 80.7 (1×MVA) and 125.3 (2×MVA), higher than after primary vaccination and comparable to boosted HSPX+ subjects. Six months after boosting, GMTs were 25.6 (1×MVA) and 49.3 (2×MVA). No safety concerns were identified.

CONCLUSION: Anamnestic responses without sustained high nAb titers support presence of durable immunological memory following MVA-BN immunization.