Safety, tolerability, immunogenicity, and plasmapheresis-based antibody collection in a phase 1b open label trial of two investigational monovalent chimpanzee adenoviral vectored filovirus vaccines, cAd3-Sudan and cAd3-Marburg, in healthy adults.

Abstract

Background: Sudan virus and Marburg virus are high priority biological threat pathogens with fatality rates of 25-90%. Recent outbreaks in Uganda, Equatorial Guinea, and Rwanda between 2022 and 2025 emphasise the critical need for effective vaccines. The aim of this phase 1b study was to determine clinical safety, tolerability, and immunogenicity of these monovalent vaccines. Plasmapheresis was used to collect hyper-immune plasma for use in future assay standardisation.

Methods: Participants received a single intramuscular injection of either cAd3-Sudan or cAd3-Marburg at 1 × 10¹¹ particle units/dose and were followed up for 181 ± 14 days. The trial was single arm with respect to each vaccine. Primary safety and tolerability endpoints were assessed in all subjects by reactogenicity for initial 7 days, adverse events for the first 28 days, and serious adverse events (SAEs) throughout the study. Secondary immunogenicity endpoints included evaluation of binding antibodies against the viral glycoproteins as measured by ELISA.

Findings: Thirty-two healthy adults were enrolled in the trial; the most commonly reported signs within 7 days of vaccination were mild headache and mild or moderate myalgia. No SAEs or deaths were reported. Binding antibodies (IgG) persisted at 9 weeks in all subjects in both groups; time to seroconversion was 14 days in both groups; peak IgG response across study participants was achieved by Day 29.

Interpretation: These vaccines are safe, immunogenic and rapidly induced glycoprotein-specific antibody responses in all participants.

Funding: Funding was provided by the Biomedical Advanced Research and Development Authority (BARDA), USA, under contract 75A50119C00055.