Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine

Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) as a smallpox and mpox vaccine has been approved in its liquid-frozen (LF) formulation in the US, Canada, and EU. A freeze-dried (FD) formulation may offer additional benefits, such as a longer shelf life and reduced dependence on cold chain storage...

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Main Authors: Richard N. Greenberg, Darja Schmidt, Daniela Reichhardt, Siegfried Roesch, Sanja Vidojkovic, Jane Maclennan, Liddy M. Chen, Robert Gruenert, Christian Kreusel, Heinz Weidenthaler, Thomas P.H. Meyer, Paul John Chaplin
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Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Human Vaccines & Immunotherapeutics
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Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2024.2384189
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author Richard N. Greenberg
Darja Schmidt
Daniela Reichhardt
Siegfried Roesch
Sanja Vidojkovic
Jane Maclennan
Liddy M. Chen
Robert Gruenert
Christian Kreusel
Heinz Weidenthaler
Thomas P.H. Meyer
Paul John Chaplin
author_facet Richard N. Greenberg
Darja Schmidt
Daniela Reichhardt
Siegfried Roesch
Sanja Vidojkovic
Jane Maclennan
Liddy M. Chen
Robert Gruenert
Christian Kreusel
Heinz Weidenthaler
Thomas P.H. Meyer
Paul John Chaplin
author_sort Richard N. Greenberg
collection DOAJ
description Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) as a smallpox and mpox vaccine has been approved in its liquid-frozen (LF) formulation in the US, Canada, and EU. A freeze-dried (FD) formulation may offer additional benefits, such as a longer shelf life and reduced dependence on cold chain storage and transport. In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety, and reactogenicity. Non-inferiority of the immune response was assessed by the 95% CI of the geometric mean ratios. Both formulations induced robust vaccinia-specific humoral and cellular immune responses. At peak humoral responses (Week 6), geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At peak cellular responses (Week 2), geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly more local reactions in the FD group. No vaccine-related serious adverse events (SAEs) or vaccine-related AE of special interest were reported. The FD formulation of MVA-BN was shown to be equivalent to MVA-BN LF.
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spelling doaj-art-9dfbc757892c4d0a9cd1e16270fc036e2025-08-20T02:16:46ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2384189Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccineRichard N. Greenberg0Darja Schmidt1Daniela Reichhardt2Siegfried Roesch3Sanja Vidojkovic4Jane Maclennan5Liddy M. Chen6Robert Gruenert7Christian Kreusel8Heinz Weidenthaler9Thomas P.H. Meyer10Paul John Chaplin11Division of Infectious Diseases, University of Kentucky School of Medicine, Lexington, KY, USAClinical Testing, Quality Control Munich, Bavarian Nordic GmbH, Martinsried, GermanyClinical Operations, CatalYm GmbH, Martinsried, GermanyClinical Operations, Topas Therapeutics GmbH, Hamburg, GermanyClinical Testing, Quality Control Munich, Bavarian Nordic GmbH, Martinsried, GermanyClinical Testing, Quality Control Munich, Bavarian Nordic GmbH, Martinsried, GermanyClinical Biometrics, Bavarian Nordic Inc, Durham, NC, USAClinical Testing, Quality Control Munich, Bavarian Nordic GmbH, Martinsried, GermanyClinical Testing, Quality Control Munich, Bavarian Nordic GmbH, Martinsried, GermanyClinical Testing, Quality Control Munich, Bavarian Nordic GmbH, Martinsried, GermanyInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, Munich, GermanyExecutive Management, Bavarian Nordic A/S, Hellerup, DenmarkModified Vaccinia Ankara Bavarian Nordic (MVA-BN) as a smallpox and mpox vaccine has been approved in its liquid-frozen (LF) formulation in the US, Canada, and EU. A freeze-dried (FD) formulation may offer additional benefits, such as a longer shelf life and reduced dependence on cold chain storage and transport. In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety, and reactogenicity. Non-inferiority of the immune response was assessed by the 95% CI of the geometric mean ratios. Both formulations induced robust vaccinia-specific humoral and cellular immune responses. At peak humoral responses (Week 6), geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At peak cellular responses (Week 2), geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly more local reactions in the FD group. No vaccine-related serious adverse events (SAEs) or vaccine-related AE of special interest were reported. The FD formulation of MVA-BN was shown to be equivalent to MVA-BN LF.https://www.tandfonline.com/doi/10.1080/21645515.2024.2384189Modified vaccinia Ankarasmallpoxmonkeypoxmpoxvaccinefreeze-dried
spellingShingle Richard N. Greenberg
Darja Schmidt
Daniela Reichhardt
Siegfried Roesch
Sanja Vidojkovic
Jane Maclennan
Liddy M. Chen
Robert Gruenert
Christian Kreusel
Heinz Weidenthaler
Thomas P.H. Meyer
Paul John Chaplin
Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine
Human Vaccines & Immunotherapeutics
Modified vaccinia Ankara
smallpox
monkeypox
mpox
vaccine
freeze-dried
title Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine
title_full Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine
title_fullStr Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine
title_full_unstemmed Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine
title_short Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine
title_sort equivalence of freeze dried and liquid frozen formulations of mva bn as smallpox and mpox vaccine
topic Modified vaccinia Ankara
smallpox
monkeypox
mpox
vaccine
freeze-dried
url https://www.tandfonline.com/doi/10.1080/21645515.2024.2384189
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