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

Sharon E. Frey, Saint Louis University Center for Vaccine Development, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.
Lindsey R. Baden, Brigham and Women's Hospital, Division of Infectious Diseases, Harvard Medical School, Boston, MA, USA.
Hana M. El Sahly, Baylor College of Medicine, Departments of Molecular Virology & Microbiology and Medicine, Houston, TX, USA.
Richard T. Davey, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Paulina A. Rebolledo, Hope Clinic, Emory Vaccine Center, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
David J. Diemert, George Washington Vaccine Research Center, Department of Medicine, George Washington University, Washington, DC, USA.
Susan J. Little, Division of Infectious Diseases & Global Public Health, University of California San Diego, San Diego, CA, USA.
C Buddy Creech, Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Zacharoula Oikonomopoulou, Saint Louis University Center for Vaccine Development, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.
Amy C. Sherman, Brigham and Women's Hospital, Division of Infectious Diseases, Harvard Medical School, Boston, MA, USA.
Jennifer A. Whitaker, Baylor College of Medicine, Departments of Molecular Virology & Microbiology and Medicine, Houston, TX, USA.
Nadine G. Rouphael, Hope Clinic, Emory Vaccine Center, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
Aimee Desrosiers, George Washington Vaccine Research Center, Department of Medicine, George Washington University, Washington, DC, USA.
Thomas C. Martin, Division of Infectious Diseases & Global Public Health, University of California San Diego, San Diego, CA, USA.
Stephanie L. Rolsma, Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Bernard Hoet, Bavarian Nordic Belgium, Brussels, Belgium.
Amy Watanabe, The Emmes Company, LLC, Rockville, MD, USA.
Anna Jaunarajs, The Emmes Company, LLC, Rockville, MD, USA.
Bernard Moss, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Kay M. Tomashek, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Andrea Lerner, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
John H. Beigel, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Document Type

Journal Article

Publication Date

11-29-2025

Journal

Vaccine

Volume

69

DOI

10.1016/j.vaccine.2025.127959

Keywords

Clade; Dose-de-escalation; Intradermal; MVA-BN; Mpox; Vaccinia

Abstract

INTRODUCTION: 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 × 10 TCID (2 × 10 ID), ID 1 × 10 TCID (1 × 10 ID), or standard dose subcutaneous (SC) 1 × 10 TCID (1 × 10 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), and safety. RESULTS: Day 43 non-inferiority by PRNT GMT was established for the 2 × 10 ID regimen but not the 1 × 10 ID regimen. The 2 × 10 ID regimen was also non-inferior to the SC dose at Days 15 and 29, prior to the second dose; the 1 × 10 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 × 10 ID regimen, but not the 1 × 10 ID regimen, was non-inferior to the SC regimen on Day 43. The study supports use of the 2 × 10 ID regimen if needed. CLINICALTRIALS: govNCT05512949.

Department

Medicine

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