Safety of MVA-BN vaccine in health-care personnel in DR Congo: a prospective cohort study.

Abstract

Modified vaccinia Ankara-Bavarian Nordic (MVA-BN) is a third-generation, replication-deficient, smallpox and mpox vaccine that is prepared in liquid and lyophilised formulations. DR Congo reports the highest number of mpox cases annually. Safety data on MVA-BN are available from high-income countries, but comprehensive safety evaluations of MVA-BN are limited in the African continent. From Feb 23 to Aug 29, 2017, and from Aug 15 to Sept 17, 2019, 1600 adult (aged 18 years and older) health-care personnel (eg, physicians, nurses, and technicians) at risk for mpox in the Tshuapa province and in Kinshasa were enrolled in an investigational prospective cohort study to evaluate safety of the two-dose MVA-BN vaccine series. Participants were excluded if they were pregnant, acutely ill, involved in another research study or had vaccine administration in the past 28 days, or had conditions that could have put the participant at an unacceptable risk. 1000 (62·5%) participants were administered the liquid formulation and 600 (37·5%) participants were administered the reconstituted lyophilised formulation. Vaccine doses were given on study days 0 and 28 and participants followed up at specified timepoints for up to 2 years for serological monitoring (14, 28, 42, 180, 365, 545, and 730 days). Participants were evaluated for immediate vaccine reactions, given adverse event diaries to document specific adverse events for 7 days following vaccine administration, and asked about potential adverse events at later timepoints up to the 2-year mark. The primary outcome was to assess the safety of MVA-BN for up to 2 years across formulations in a population at increased risk of mpox. This study is registered with ClinicalTrials.gov (NCT02977715). There was no significant difference in the risk of an adverse event between the liquid formulation (488 [49·0%] of 995 participants) and lyophilised formulation (315 [53·7%] of 586 participants; adjusted risk ratio [aRR] 1·08 [95% CI 0·98-1·19]) within 7 days after vaccination. Within 7 days of vaccine administration, participants had similar proportions of local injection-site reactions between the liquid (356 [35·7%] of 995 participants) and lyophilised (213 [36·3%] of 586 participants) formulations, but those who received the lyophilised formulation had a higher risk for systemic symptoms than those who received the liquid formulation (aRR 1·20 [95% CI 1·05-1·37]). 18 serious adverse events, including 17 deaths and one stillbirth, occurred within the 2-year study period; safety monitors (two board-certified physicians: one in the USA and one in DR Congo) deemed none of the events were causally associated with vaccine administration. 14 pregnancies occurred within 1 month of vaccination and 13 resulted in the birth of healthy infants. This study adds to the growing body of literature on the safety of MVA-BN in different populations. Although limited by incomplete grading of specific adverse events, low numbers of pregnant participants, and differences in health-care access and infrastructure, the data from this cohort in DR Congo do show good safety outcomes for up to 2 years with both liquid and lyophilised vaccine formulations. Because MVA-BN vaccination campaigns are crucial to clade I and clade II mpox outbreak responses, the data from this study supporting safety of MVA-BN in this population are key to build vaccine confidence. US Centers for Disease Control and Prevention and the US Biomedical Advanced Research and Development Authority. For the French translation of the abstract see Supplementary Materials section.