Safety and immunogenicity of a recombinant vesicular stomatitis virus-based Sudan virus vaccine in adults in the USA: a single-blind, first-in-human, dose-escalation phase 1 clinical trial.

BACKGROUND: A vaccine is needed to prevent Sudan virus (SUDV) disease (SVD), a haemorrhagic fever. We report a first-in-human clinical trial evaluating the safety and immunogenicity of a recombinant vesicular stomatitis virus (rVSV) vaccine expressing the SUDV envelope glycoprotein (rVSVΔG-SEBOV-GP). METHODS: In this single-blind, placebo-controlled, dose-escalation phase 1 trial, adults (18-50 years) in good general health and without previous exposure to VSV-vectored vaccines or any haemorrhagic fever, were enrolled at two clinical research sites in Texas, USA. Participants received a single intramuscular dose of rVSVΔG-SEBOV-GP at 2 × 106, 2 × 107, or 2 × 108 plaque-forming units, or placebo. Dose groups were enrolled sequentially, from the lowest to the highest dose. In each dose group, the first two participants (sentinels) received the vaccine without randomisation; the remaining were randomised (4:1 vaccine-to-placebo ratio, for a final vaccine-to-placebo ratio of 5:1). Only participants were masked. Primary outcomes, assessed on all participants, were safety and tolerability assessments, based on local and systemic reactions within 14 days, and vaccine-related serious adverse events and adverse events of special interest for the entire trial. Secondary outcome was the evaluation of humoral immunity, assessed by anti-SUDV-GP IgG and serum neutralising activity against SUDV-GP at baseline and 28, 84, and 168 days after vaccination. This study (now completed) is registered at ClinicalTrials.gov (NCT05724472). FINDINGS: Between June 19, 2023, and July 21, 2023, 36 participants (20 [56%] women; median age 37 years [IQR=12·2]) were enrolled and received a single intramuscular injection of vaccine (n=10 per dose group) or placebo (n=6); all vaccine recipients completed 6 months of follow-up. 31 (86%) of 36 (vaccine 26 [87%] of 30; placebo five [83%] of six) participants had solicited adverse events; the proportions were similar across all dose groups. Most participants (vaccine 22 [73%] of 30; placebo five [83%] of six) had local pain and tenderness, mild to moderate, but severe in one participant (2 × 108 plaque-forming units). Systemic reactions occurred in 25 (83%) of 30 vaccine recipients and four (67%) of six placebo recipients. Severe transient reactions were reported by one (17%) of six placebo recipients (joint pain) and four (13%) of 30 vaccine recipients (combinations of malaise, chills, myalgia, abdominal pain, headache, and nausea). Antibody responses, present by day 29 and beyond, were similar at all dosages, and maintained in all participants by month 6. By the end of the study, neutralising activity was detected in 20 (67%) of 30 vaccinees and correlated to binding IgG. INTERPRETATION: rVSVΔG-SEBOV-GP was well tolerated and immunogenic at all the three doses studied. These findings support its further development for prevention of SVD. FUNDING: Biomedical Advanced Research and Development Authority.