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Evaluation of the safety and immunogenicity of two fractional intradermal regimens of MVA-BN compared to standard dose vaccination

12/2025

Journal Article

Authors:
Frey, S. E.; Baden, L. R.; El Sahly, H. M.; Davey, R. T.; Rebolledo, P. A.; Diemert, D. J.; Little, S. J.; Creech, C. B.; Oikonomopoulou, Z.; Sherman, A. C.; Whitaker, J. A.; Rouphael, N. G.; Desrosiers, A.; Martin, T. C. S.; Rolsma, S. L.; Hoet, B.; Watanabe, A.; Jaunarajs, A.; Moss, B.; Tomashek, K. M.; Lerner, A.; Beigel, J. H.; Dmid Study Group

Volume:
69

Journal:
Vaccine

PMID:
41319397

URL:
https://www.ncbi.nlm.nih.gov/pubmed/41319397

DOI:
10.1016/j.vaccine.2025.127959

Keywords:
Clade Dose-de-escalation Intradermal Mva-bn Mpox Vaccinia

Abstract:
NTRODUCTION: Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is being used to mitigate disease in the current global mpox outbreak, but a global vaccine shortage may limit large scale vaccination. METHODS: Participants were randomized 1:1:1 to receive two doses of MVA-BN administered 28 days apart: intradermal (ID) 2 x 10(7) TCID(50) (2 x 10(7) ID), ID 1 x 10(7) TCID(50) (1 x 10(7) ID), or standard dose subcutaneous (SC) 1 x 10(8) TCID(50) (1 x 10(8) ID). The primary objective was non-inferiority testing of each ID regimen compared to the standard SC regimen using vaccinia virus plaque reduction neutralizing titer assay (PRNT) geometric mean titers (GMT) at Day 43 (2 weeks post-second vaccination). Secondary objectives were non-inferiority testing of individual peak humoral immune responses, comparison of humoral immune responses, vaccinia virus-specific PRNT half-life (t((1/2))), and safety. RESULTS: Day 43 non-inferiority by PRNT GMT was established for the 2 x 10(7) ID regimen but not the 1 x 10(7) ID regimen. The 2 x 10(7) ID regimen was also non-inferior to the SC dose at Days 15 and 29, prior to the second dose; the 1 x 10(7) ID regimen did not meet the non-inferiority criteria at any point post-vaccination. The three study regimens had similarly high seroconversion rates and similar anti-vaccinia PRNT half-lives. Most participants experienced injection site and systemic reactogenicity of moderate severity or less and only mild unsolicited adverse events (mostly skin discoloration and nodules at the injection site). CONCLUSION: The 2 x 10(7) ID regimen, but not the 1 x 10(7) ID regimen, was non-inferior to the SC regimen on Day 43. The study supports use of the 2 x 10(7) ID regimen if needed. CLINICALTRIALS: govNCT05512949.

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