Marburg virus (MARV) is a virus of high human consequence with a case fatality rate of 24–88%. The global health and national security risks posed by Marburg virus disease (MVD) underscore the compelling need for a prophylactic vaccine, but no candidate has yet reached regulatory approval. Here, we evaluate a replication-defective chimpanzee adenovirus type 3 (ChAd3)-vectored MARV Angola glycoprotein (GP)-expressing vaccine against lethal MARV challenge in macaques. The ChAd3 platform has previously been reported to protect against the MARV-related viruses, Ebola virus (EBOV) and Sudan virus (SUDV), and MARV itself in macaques, with immunogenicity demonstrated in macaques and humans. In this study, we present data showing 100% protection against MARV Angola challenge (versus 0% control survival) and associated production of GP-specific IgGs generated by the ChAd3-MARV vaccine following a single dose of 1 × 10¹¹ virus particles prepared in a new clinical formulation buffer designed to enhance product stability. These results are consistent with previously described data using the same vaccine in a different formulation and laboratory, demonstrating the reproducible and robust protective efficacy elicited by this promising vaccine for the prevention of MVD. Additionally, a qualified anti-GP MARV IgG ELISA was developed as a critical pre-requisite for clinical advancement and regulatory approval.

The FDA Animal Rule was devised to facilitate approval of candidate vaccines and therapeutics using animal survival data when human efficacy studies are not practical or ethical. This regulatory pathway is critical for candidates against pathogens with high case fatality rates that prohibit human challenge trials, as well as candidates with low and sporadic incidences of outbreaks that make human field trials difficult. Important components of a vaccine development plan for Animal Rule licensure are the identification of an immune correlate of protection and immunobridging to humans. The relationship of vaccine-induced immune responses to survival after vaccination and challenge must be established in validated animal models and then used to infer predictive vaccine efficacy in humans via immunobridging. The Sabin Vaccine Institute is pursuing licensure for candidate filovirus vaccines via the Animal Rule and has convened meetings of key opinion leaders and subject matter experts to define fundamental components for vaccine licensure in the absence of human efficacy data. Here, filoviruses are used as examples to review immune correlates of protection and immunobridging. The points presented herein reflect the presentations and discussions during the second meeting held in October 2021 and are intended to address important considerations for developing immunobridging strategies.

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. 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. 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. These vaccines are safe, immunogenic and rapidly induced glycoprotein-specific antibody responses in all participants. Funding was provided by the Biomedical Advanced Research and Development Authority (BARDA), USA, under contract 75A50119C00055.