VacICoP: Chimpanzee Adenovirus Type 3-Vectored Marburg Glycoprotein (GP)-Expressing Vaccine (ChAd3-MARV)-Induced Correlates of Protection (360G-Wellcome-308739_Z_23_Z)

Marburg Virus disease (MVD) outbreaks in Europe and Africa highlight the urgent need for vaccines. This study will increase the breadth of the ICoPs discovery effort, hypothesizing that early, emerging, and sustained Fab- and Fc-mediated effector polyfunctionality are crucial determinants of protection. Objectives include characterizing antibodies, dissecting immunity determinants and developing unbiased ICoPs selection algorithms. With unique access to relevant samples and cutting-edge immunology, we will broaden ICoPs exploration beyond one antigen, generating correlate(s) with broader utility. Our diverse specimen resource includes NHP and clinical samples from the USA, Kenya, and Uganda, survivor and deceased sera with clinical data, and healthy subjects' sera from diverse demographics. Robust validated assays, international standard reagents and protocols will ensure consistency. Through five interlinked work-packages, we will screen specimens for Fab- and Fc- mediated functions, analyze T-cell functions, validate targets of antibody- mediated protection, discover protection-linked biomarkers, and integrate data for ICoPs down-election. Key deliverables include defining ChAd3-MARV ICoPs, scalable screening assays, reference reagents, and licensure guidance. Our proposal aligns with global MVD vaccine efforts to address this critical public health challenge. Capacity building engagements and trainings for key stakeholders like local regulatory bodies, Ministry of Health and the community will be undertaken.