Periodic Reporting for period 1 - MARVAX (Development of novel viral vectored vaccines against Marburgviruses inducing robust and cross-reactive protection)
Période du rapport: 2023-12-01 au 2025-05-31
Marburg virus (MARV), a member of the Filoviridae family alongside Ebola virus (EBOV), is a highly pathogenic agent capable of causing severe and often fatal illness. The increasing frequency and geographical spread of MARV outbreaks, including recent cases in Central and Eastern Africa, confirm its epidemic potential and its growing threat to global health. Despite its prioritisation by the World Health Organization (WHO), there are currently no licensed vaccines available to prevent MARV infection and disease, resulting in high morbidity and mortality rates during outbreaks.
The EU-funded MARVAX project aims to address this critical medical threat by developing safe, effective, and scalable vaccine candidates against MARV, using the measles virus (MV) and modified Vaccinia Ankara (MVA) vector platforms. The vaccine candidates, displaying multiple MARV antigens, will undergo comprehensive evaluation of their induced humoral and cellular immune responses in preclinical animal models, including innovative in-vitro platforms and relevant in-vivo animal models. Ultimately, the project will produce vaccines suitable for transition into potential phase I clinical trials, contributing to global preparedness against future filovirus outbreaks.
The EU-funded MARVAX project aims to address this critical medical threat by developing safe, effective, and scalable vaccine candidates against MARV, using the measles virus (MV) and modified Vaccinia Ankara (MVA) vector platforms. The vaccine candidates, displaying multiple MARV antigens, will undergo comprehensive evaluation of their induced humoral and cellular immune responses in preclinical animal models, including innovative in-vitro platforms and relevant in-vivo animal models. Ultimately, the project will produce vaccines suitable for transition into potential phase I clinical trials, contributing to global preparedness against future filovirus outbreaks.
MARVAX is progressing toward the development and characterization of measles virus (MV)- and modified vaccinia virus Ankara (MVA)-based vaccine candidates targeting MARV, with the aim to develop multivalent vaccines encoding for and expressing multiple MARV antigens, to elicit broad, cross-reactive immune responses within the Orthomarburgvirus genus. The antigens were selected based on their immunogenic potential and conservation across MARV variants, aiming to stimulate both cellular and humoral immune responses against MARV. Within the first reporting period, the MARVAX consortium successfully engineered MV-based vaccine candidates expressing up to three MARV (Musoke variant) antigens and MVA-based vaccine candidates expressing up to two MARV antigens. Currently, the project is finalizing the development of MVA-based vaccine candidates co-expressing three MARV antigens, and testing the immunogenicity induced by all generated candidates as standalone vaccines or in prime/boost combinations, in cell systems as well as in small animal models. The ongoing experiments will inform the down-selection of the most promising vaccine prototypes for further preclinical development.
The family Filoviridae includes single-stranded RNA viruses that are among the most pathogenic viruses known to humans. Among these, EBOV and MARV are prominent human pathogens that have caused unpredictable, severe disease outbreaks in equatorial African countries. Currently, licensed medical countermeasures (MCMs), such as vaccines and therapeutics, are available for EBOV, but none of these offer cross-protection against other members of the Filoviridae family including MARV. The reason for this lack of cross reactivity is that current vaccines and antibody-based post-exposure therapies are directed against the virus GP, which shows high variability between species at the amino acid level. Thus, while highly valuable and successful, current EBOV vaccines cannot be used in the event of, for example, a MARV disease outbreak. Of note, MARV disease has been recently detected in countries with no previous history of outbreaks such as Ghana, Rwanda and Tanzania. These results suggest that the geographical distribution of MARV is greater than previously thought or expanding and call for urgent development of broader-acting MCMs.
MARVAX addresses this need by developing innovative next-generation vaccines that target not only the GP, but also additional epitopes that are highly conserved across filoviruses. For example, the inclusion of the NP enables the presentation of T-cell epitopes that are conserved across all Orthomarburgviruses (e.g. MARV and Ravn virus) as well as across all ebolaviruses (such as EBOV, Sudan virus, etc.), thus broadening cross-reactive cellular immunity. In addition, antigens like VP40, in combination with GP, can self-assemble into virus-like particles (VLPs), potentially enhancing immunogenicity and mimicking native viral structures more effectively. By introducing multiple antigens into its MV- and MVA-based vaccine candidates, MARVAX goes beyond the state of the art in its vaccine design and has the potential of impacting our ability to respond to future filovirus outbreaks regardless of the specific etiological agent identified. To ensure uptake, the project will advance preclinical data, IP protection, and explore regulatory and industrial pathways toward clinical translation.
MARVAX addresses this need by developing innovative next-generation vaccines that target not only the GP, but also additional epitopes that are highly conserved across filoviruses. For example, the inclusion of the NP enables the presentation of T-cell epitopes that are conserved across all Orthomarburgviruses (e.g. MARV and Ravn virus) as well as across all ebolaviruses (such as EBOV, Sudan virus, etc.), thus broadening cross-reactive cellular immunity. In addition, antigens like VP40, in combination with GP, can self-assemble into virus-like particles (VLPs), potentially enhancing immunogenicity and mimicking native viral structures more effectively. By introducing multiple antigens into its MV- and MVA-based vaccine candidates, MARVAX goes beyond the state of the art in its vaccine design and has the potential of impacting our ability to respond to future filovirus outbreaks regardless of the specific etiological agent identified. To ensure uptake, the project will advance preclinical data, IP protection, and explore regulatory and industrial pathways toward clinical translation.