Development of novel viral vectored vaccines against Marburgviruses inducing robust and cross-reactive protection

The frequency, magnitude, and geographical range of Marburg virus disease outbreaks are expanding, with recent cases emerging in Equatorial Guinea and Tanzania. Marburgviruses, listed among the WHO priority pathogens, have demonstrated their epidemic potential. However, no licensed vaccines are available, and outbreaks continue to impose high morbidity and mortality burdens. Vaccine candidates in the pipeline are based on the Marburg virus (MARV) glycoprotein (GP) as a single immunogen. MARVAX ambition is to improve the strength and breadth of MARV vaccines by deploying the measles virus (MV) and modified vaccinia virus Ankara (MVA) viral vector vaccine platforms for expression of several MARV antigens: GP, viral protein 40 (VP40), which together with GP allows the formation of virus-like particles, and the nucleoprotein (NP), which contains conserved epitopes that are the main drivers of T cell responses. We will evaluate in depth the innate, adaptive and memory antigen-specific humoral and cellular cross-protective immune responses induced by MV-MARV and MVA-MARV vaccine candidates against MARV, Ravn virus and ebolaviruses, in single dose and in homologous and heterologous prime/boost immunization regimens, through an innovative preclinical testing pipeline. We will use cutting-edge and novel in vitro primary human cell co-cultures and immunocompetent mouse models to evaluate immunogenicity, chimeric and avatar mouse models to evaluate immunogenicity and efficacy and identify correlates of protection, and the highly relevant cynomolgus macaque model to evaluate safety, immunogenicity and efficacy. Furthermore, GMP batches of the best vaccine candidates will be produced by the end of the project, towards their future evaluation in a phase I clinical trial, in collaboration with the WHO-led initiative for prioritization and acceleration of clinical trials of Marburgvirus vaccines in at-risk and healthcare communities and upon outbreaks.