The highly contagious SARS-CoV-2 virus has generated an unprecedented pandemic with global dramatic public health and socio-economic consequences need an urgent mitigation. Despite the progression of the global use of efficient vaccines, an increased transmissibility of variants of concern (VOC) is predominantly observed. The reduced sensitivity of VOCs to neutralizing response could become a serious obstacle for efficient vaccination. In the absence of approved specific antiviral therapies for vaccinated-non-responders and the scarce anti-inflammatory therapies, passive immunotherapies with polyclonal immunoglobulins could be considered a part of the solution. The main objective of EPIC-CROWN is to rapidly assess, in multicentric clinical trials (phase IIa, 16 patients and IIb, 400 patients), an EMA-authorized antiviral immunotherapy based on potent and broad equine neutralizing anti-SARS-CoV-2 polyclonal F(ab’)2 antibodies in COVID-19 patients, including VOC carriers. In order to save lives and reduce the use and costs of critical care, this therapeutic solution expect to reduce at least by 50% ICUs admissions and a highly significant mortality rate of treated patients. To optimize the indications for the treatment, potency and breath of F(ab’)2 against variants will be assessed in in vitro and in an animal model as well as prospective studies will respectively be done on immune assessment in treated patients and on mitigation of exacerbated immune responses in vivo. Fab’entech will coordinate EPIC-CROWN-2 formed by outstanding experts in different project domains that include clinical trials (HISS, Greece), virology (IMAS12, Spain), and immunopathology models and mitigation (BNITM, Germany - IRD, France). Most of them having already been working together in European projects. Importantly, EPIC-CROWN-2 will be integrated as part of both the large European trial network EU-RESPONSE and the multinational European Adaptive Platform Trial “Solid Act".

The SUPPORT project aims to strengthen health research systems in sub-Saharan African (SSA) countries affected by poverty-related pediatric infectious diseases. This goal will be achieved through a comprehensive fellowship program designed to train and mentor early and mid-career researchers. The consortium comprises clinical research institutions, academia, and stakeholders from both SSA and Europe. Makerere University in Uganda will act as the scientific leadership hub, with fellows stationed at leading SSA research institutions, fostering South-to-South collaboration. Additionally, short-term internships at European institutions will complement their training. The selection of target host countries, including Mozambique, Uganda, Zambia, Zimbabwe, and Senegal, was based on their research capacity needs and disease burden, encompassing Anglophone, Francophone, and Lusophone nations. The impact of SUPPORT will be the establishment of a competent and innovative community of scientists and healthcare professionals equipped to actively investigate and address pediatric infectious diseases, including epidemic management, in SSA. By strengthening research capacity and promoting collaboration, the project contributes to long-term improvements in morbidity and mortality associated with infectious diseases in children from low- and middle-income countries (LMICs). SUPPORT will train 8 early-career fellows and 5 mid-career fellows, developing a new collaborative clinical study based on two ongoing EDCTP projects, EMPIRICAL and UNIVERSAL. The fellows will undergo a rigorous training program that combines online and face-to-face components to develop essential research skills. This training will be integrated with their individual research projects, which address critical research questions related to pediatric infectious diseases in SSA. The fellows will take the lead on these projects with guidance and support from mentors affiliated with African and European institutions.

The recent outbreak of Ebola virus (EBOV), in particular the EBOV Sudan strain, is a major cause for concern as there are currently no available vaccines and treatments for this fatal disease. Moreover, surveillance measures are suboptimal and the social response to viral outbreaks hindered by limited acceptance of countermeasures. The Ebola PREP-TBOX consortium aims to make significant strides in developing essential tools and strategies for effective surveillance response, and control of Ebola outbreaks, fostering a safer and resilient future. Our objective is to build a toolbox permitting earliest Ebola outbreak containment. A spatiotemporal model utilizing environmental, animal reservoir, socioeconomic and human movement data will be developed enabling prediction of future outbreaks. The sensitivity of current diagnostics will be improved through innovative viral capture techniques. EBOV exposure and immune response will be tested from human-animal interface samples from the Republic of Congo (RoC), Democratic Republic of Congo (DRC) and Uganda. New treatments for the EBOV Sudan strain will be developed by testing for broad-spectrum activity of the EBOV anti-Zaire Equine polyclonal antibody. Further, development of mosaic antigens, composed of several filovirus strains (incl. EBOV), will create new tools for broad-spectrum vaccine and therapeutic development. Conductance of knowledge, attitude and practice (KAP) studies, gap analysis and targeted trainings in RoC, DRC and Uganda will improve population acceptance for future EBOV outbreak interventions. The training of African researchers by the consortium will increase local skills and competences. Ebola PREP-TBOX is an interdisciplinary and complementary consortium including partners from the Congo Basin (FCRM-RoC, INRB-RDC, UVRI-IAVI-Uganda), Prof. JJ Muyembé (Ebola discoverer 1976) and partners from Europe (Fabentech and Bacfly/CNRS-France, IMAS12-Spain) and the support of G Kobinger (GNL,US).

e-FabRIC will develop a new hyperimmunization strategy for generating high titers equine immunoglobulins having a broad neutralizing specificity against viral targets belonging to same subfamily phylogenic tree. The viral subfamily selected to demonstrate the unique benefits of this innovative way to induce highly anti-viral active antibodies is the sarbecovirus subfamily. The equine antibodies will be processed as purified F(ab’)2 fragments, a well-known pharmaceutical product with a strong historical safety record in human patients. The F(ab’)2 antibody fragments generated by e-FabRIC are expected to display a unique and very wide neutralizing activity spectrum. This new property will be the synergistic outcome of the immunization with a nanoparticle co-displaying 8 different sarbecovirus RBD subunits (designated as “mosaic antigen”) and the natural immunogenetic diversity present in individual horses. In each individual horse, the mosaic antigen immunization will drive the generation and maturation of antibodies highly focused on conserved epitope structures shared by the different sarbecovirus RBD subunits and associated with viral neutralization. As each horse's own immunogenetics will mature the mosaic antigen-specific antibodies in a different way, several equine individual antibody specificities will be pooled in order to expand the overall broad viral neutralizing activity of the final pharmaceutical product. The combined multiplicity of individual antibody response diversities and the highly focused antibody responses induced by the mosaic antigen will be the basis of a broadly potent, immunotherapy pharmaceutical F(ab’)2-based product able to significantly reduce the clinical and societal impact of any emergence of a new human sarbecovirus outbreak. The scientific and technical learnings of this new and powerful immunization strategy will be applicable to other viral families from which human infectious threats may arise.