Pregnant women in Africa are exposed to considerable health risks, with parasitic infections being a major threat. Schistosomes, soil-transmitted helminths, and malaria parasites are highly prevalent and polyparasite infections are common. In pregnancy, besides iron deficiency parasites are a key factor causing anaemia associated with an increased risk of maternal and infant morbidity and mortality. More than 50% of the pregnant women are affected by anaemia and an estimated 0.8 million pregnant women globally have severe anaemia. Antenatal care is a health program to regularly deliver health services including preventive measures with the aim of improving maternal and newborn health. In terms of fighting parasitic diseases, WHO recommends to preventively treat soil-transmitted helminths, schistosomes and malaria parasites. In many endemic sub-Saharan African countries, however, these recommendations are often only partially implemented and not consistently applied in daily antenatal care. Reasons are multifactorial but hesitation in administering multiple drugs this vulnerable population and the complexity of integrating the use of multiple drugs into the antenatal care schedule. On the other hand, data is accumulating that outweighs the potential risk of antiparasitic drug intake versus health benefits. The project aims to increase the uptake and integration of presumptive antiparasitic treatment during pregnancy to combat anaemia and improve health outcomes for pregnant women and their babies in sub-Saharan Africa. To this end, a multi-country trial will assess the safety, tolerability and efficacy of co-administered antiparasitic drugs. Pharmacokinetic data, cost-effectiveness analysis and public health stakeholder’s involvement will further strengthen the case for future implementation of co-administered antiparasitic drugs in antenatal care schedules. Training in African scientific leadership will contribute to a critical mass of highly trained professionals.

The ISIDORe consortium, made of the capacities of European ESFRI infrastructures and coordinated networks, proposes to assemble the largest and most diverse research and service providing instrument to study infectious diseases in Europe, from structural biology to clinical trials. Giving scientists access to the whole extent of our state of the art facilities, cutting edge services, advanced equipment and expertise, in an integrated way and with a common goal, will enable or accelerate the generation of new knowledge and intervention tools to ultimately help control SARS CoV 2 in particular, and epidemic prone pathogens in general, while avoiding fragmentation and duplication among European initiatives. Such a global and interdisciplinary approach is meant to allow the implementation of user projects that are larger, more ambitious and more impactful than the EU supported transnational activities that the consortium is used to run. Our proposition is ambitious but achievable in a timely fashion due to the relevance and previous experience of the partners that we have gathered and that have complementary fields of expertise, which addresses the need for an interdisciplinary effort. Leveraging all these existing strengths to develop synergies will create an additional value and enhance Europe capacity for controlling emerging or re emerging and epidemic infectious diseases, starting with the COVID 19 pandemic. Such a global and coordinated approach is consistent with the recommendations of the One Health concept and necessary to make significant contributions to solving complex societal problems like epidemics and pandemics.

DEFENDER will address the need for innovative intervention strategies against viruses with epidemic potential, by adopting a comprehensive and integrative platform approach. DEFENDER’s revolutionary Research and Innovation pipeline will focus on preventing virus entry through a host-directed bottom-up approach based on functional genetics in parallel to a top-down virus glycoprotein-centered approach. We will identify novel host dependency and restriction factors, including receptors and proteins involved in viral attachment and binding, endosomal uptake and virus genome uncoating, as targets for antiviral therapy. In parallel, we will use recombinant viral glycoproteins to identify broadly neutralizing nanobodies and novel epitopes for the AI-based design of next generation immunogens and the improvement of therapeutic antibodies. The host bottom-up functional genetic approach will be applied to Nipah, Lassa, Zika, Dengue, Yellow fever, and Chikungunya viruses. Host factors will be identified using a unique arrayed CRISPR perturbation platform, combined with advanced statistical and machine learning approaches and mathematical modelling, mechanistic experiments, and cutting-edge imaging techniques. In parallel, the virus top-down glycoprotein-centered approach will lead to the identification and structural characterization of broadly neutralizing nanobodies targeting conserved epitopes of the glycoproteins of Nipah and Lassa viruses in pre-fusion conformation. DEFENDER will deliver innovative antiviral candidates that induce target degradation, next generation immunogens, and a novel concept to improve the activity of therapeutic antibodies, with proof-of-concept preclinical evaluation in mice. It will define the most vulnerable virus-host interactions, to deliver a robust development pipeline for novel antivirals, therapeutic antibodies, and immunogens and increase antiviral options against a wide range of priority (re-) emerging viruses.