One- and Two-Dose Vaccinations With Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines

• Published in: The Journal of infectious diseases Vol. 227; no. 10; pp. 1203 - 1213
• Main Authors: Ilchmann, Heiko, Samy, Nathaly, Reichhardt, Daniela, Schmidt, Darja, Powell, Jacqueline D, Meyer, Thomas P H, Silbernagl, Günter, Nichols, Rick, Weidenthaler, Heinz, De Moerlooze, Laurence, Chen, Liddy, Chaplin, Paul
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 12.05.2023
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; Clinical trials; Humans; Immunization; Immunological memory; Immunology; Lymphocytes B; Major; Memory cells; Mpox; Smallpox; Smallpox - prevention & control; Smallpox Vaccine; Vaccination; Vaccinia; Vaccinia virus; Ankara Turkey; Turkey; memory response; monkeypox; orthopoxvirus; vaccinia experienced; revaccination; recall response; booster
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiac455

Abstract Background Although modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination is approved for smallpox and monkeypox prevention, immunological persistence and booster effects remain undescribed. Methods Participants naive 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 naive groups (approximately 75 each) received an MVA-BN booster 2 years later. Results Neutralizing antibody (nAb) geometric mean titers (GMTs) increased from 1.1 (baseline, both naive 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 naive 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. Conclusions Anamnestic responses to boosting without sustained high nAb titers support presence of durable immunological memory following primary MVA-BN immunization. Clinical Trials Registration. NCT00316524 and NCT00686582. One or 2 primary MVA BN vaccinations induced similar durable B-cell memory responses as a booster administered 2 years after primary vaccination showed rapid and robust antibody response. No safety concerns were identified following the booster.