Safety of MVA-BN in Healthcare Personnel, Democratic Republic of the Congo

Background Modified vaccinia Ankara-Bavarian Nordic (MVA-BN) is a third generation, replication- deficient, smallpox and mpox vaccine prepared in liquid and lyophilized formulations. The Democratic Republic of the Congo reports the highest number of cases of clade I mpox annually.

During the summer of 2017 and 2019, 1,600 healthcare personnel were enrolled in an investigational prospective cohort study to evaluate safety of the 2-dose MVA-BN vaccine series; 1000 were administered liquid and 600 were administered reconstituted lyophilized MVA-BN. Vaccine doses were given on study days 0 and 28 and presence or absence of adverse events were evaluated at routine follow-up appointments for up to two years.

There were 49% of liquid and 54% of lyophilized formulation participants who experienced at least one adverse event within 7 days. Eighteen serious adverse events, including seventeen deaths and one stillbirth, occurred within the 2-year study period; safety monitors deemed none were causally associated with vaccine administration. Fourteen pregnancies occurred within one month of vaccination, 13 gave birth to healthy infants.

This study adds to the growing body of literature on the safety of MVA-BN in different populations. The data from this Congolese cohort demonstrate good safety outcomes for up to two years with both liquid and lyophilized vaccine formulations. As MVA-BN vaccination campaigns are launched in endemic and surrounding countries in late 2024 as part of clade I mpox outbreak response efforts, the data from this study supporting safety of MVA-BN in an African population are crucial to build vaccine confidence. Trial registry number: NCT02977715 Competing Interest Statement The authors have declared no competing interest. Clinical Trial NCT02977715 Funding Statement Funding for this project comes from the US Centers for Disease Control and Prevention 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: The protocol received human subjects ethical and regulatory approvals from the CDC and KSPH Institutional Review Boards and was authorized by the U.S. Food and Drug Administration. This study is registered in ClinicalTrials.gov under identifier NCT02977715. See 45 C.F.R. part 46; 21 C.F.R. part 5 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 Footnotes Data Sharing: Individual de-identified participant data (including data dictionaries) will not be shared. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Funding: Funding for this project comes from the US Centers for Disease Control and Prevention Conflicts of Interest: There are no conflicts of interest to declare from the authors. Data Availability All data produced in the present work are contained in the manuscript