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 first Ebolavirus Zaire (EBOV) outbreak of 2014 was declared on 22 March in Guinea. As of 30 September 2014, the World Health Organization (WHO) reports the total number of cases in the current outbreak of Ebola virus disease (EVD) in West Africa at 7470, with 3431 deaths. The US Centers for Disease Control and Prevention states that the number of cases is currently doubling every 20 days and estimates the true number of cases at 2.5 times higher than that reported. Countries that have been affected are Guinea, Liberia, Nigeria, Senegal and Sierra Leone. Ten percent of fatalities have occurred among front line health care workers attempting to contain the epidemic. On 7 August 2014, the WHO requested that GSK “fully engage in WHO-coordinated efforts to test, license and make available safe and effective Ebola interventions” to assist in the control of the outbreak. Taking into account the early stage of development, EbolaVac seeks to accelerate the clinical development of the GSK chimpanzee adenovirus type 3 Ebolavirus Zaire (ChAd3-EBO Z) vaccine candidate to make the vaccine available to frontline health care workers at risk and to be used in the containment of EBOV outbreaks. The project specifically aims to: (i) complete Phase 1 development of the ChAd3-EBO Z vaccine by supporting a clinical study conducted in Lausanne, Switzerland (WP2); (ii) evaluate the ChAd3-EBO Z vaccine in Phase 2 testing on adults and children at established clinical study centers in West Africa outside the current most heavily affected countries of Guinea, Sierra Leone, and Liberia (WP3); (iii) investigate immunological effects of vaccination and the effect of booster vaccination (WP4) and (iv) centrally manage and analyse clinical study data (WP5). Besides using an innovative vaccine technology, much of the innovation of this program will reside in its capacity to implement vaccine evaluation under significant time pressure and complex logistical challenges while maintaining appropriate quality standards.