Equivalence of Freeze-dried and Liquid-frozen Formulations of MVA-BN as Smallpox and Mpox Vaccine

Orthopox virus-induced diseases such as smallpox and mpox (also known as monkeypox previously) remain a serious public health concern. Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) has been approved in its liquid-frozen (LF) formulation for prevention of smallpox and mpox in the US, Canada and EU. A freeze-dried (FD) formulation might confer additional benefits such as longer shelf life and less reliance on cold chain storage and transport, thus can better meet the potential challenge of large quantity vaccine deployment in emergency situations. In a phase 2 clinical trial, 651 vaccinia-naive 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. Strong vaccinia-specific humoral and cellular immune responses were induced by both formulations, with peak humoral responses at Week 6 and peak cellular responses at Week 2. At 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 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 higher 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 the LF formulation in immunogenicity, and comparable safety findings were observed from both formulations. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT01668537 ### Funding Statement The study was funded by the Biomedical Advanced Research and Development Authority (BARDA). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: - IRB of University of Kentucky, Office of Research Integrity gave ethical approval for this work. - IRB of Quorum Review gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymized data can be made available upon request. All requests must be submitted to Bavarian Nordic A/S for evaluation and approval.