marburg virus - a first in human clinical trial to deliver a vaccine against marburg virus disease

Marburg virus disease (MVD) is caused by Marburg virus which belongs to filovirdae family and is considered one of the deadliest infectious diseases, causing viral hemorrhagic fever (VHF) in humans with a case-fatality rate between up to 90%. Currently, there are no vaccines or specific treatment for MVD. Between 1967 and 2021 there have been fourteen recorded outbreaks; primarily occurring in Uganda. However, in 2022 the first MVD case was recorded in Ghana and in 2023 the first outbreak occurred in Equatorial Guinea and also in Tanzania. There is an ongoing and pressing need for effective vaccines and treatments against MVD, especially considering the continued spread into new geographical locations. However, there are a limited number of vaccine technologies which can protect against filoviruses. The licensed vaccines against Ebolavirus (of the Filoviridae family) are viral vectors. Unfortunately, the currently licensed vaccines are not effective against MVD. We have designed, pre-clinically tested and GMP produced a viral vectored vaccine against MVD using, the chimpanzee adenoviral vector (ChAdOx1). ChAds are a platform vaccine technology with wide global use against COVID-19, with ChAdOx1 nCoV-19/AZD1222 being licensed in more than 170 countries. ChAdOx1 regimens are highly immunogenic, and the emergency response against COVID-19 has led to large-scale manufacture of viral vectored vaccines at a price-point which is affordable in low- and middle-income countries (LMIC). We are seeking funds to initiate first in human (FIH) studies in the UK and to also progress challenge studies in large animal NHP models. Both deliverables are critical to progress a data package for regulatory approval. Clinical development will involve a first-in-human (phase 1) study of ChAdOx1 Marburg taking place in Oxford at The Oxford Vaccine Group (OVG). The proposed trial design will involve 51 healthy participants aged 18-55 years. There will be a lead-in cohort of 6 participants who will each receive 2 doses of vaccine, 12 weeks apart. This will be followed by a randomised, placebo controlled, participant-observer blind cohort of 45 participants, randomised to single dose, two doses or placebo only (4:4:1 randomised), 12 weeks apart. Participants will be followed up for 6 months. The primary outcomes are to assess the safety and tolerability of the vaccine, and the secondary objectives are to assess the immunogenicity.