Many HIV vaccine concepts and several efficacy trials have been conducted in the prophylactic and therapeutic fields with limited success. There is an urgent need to develop better vaccines and tools predictive of immunogenicity and of correlates of protection at early stage of vaccine development to mitigate the risks of failure. To address these complex and challenging scientific issues, the European HIV Vaccine Alliance (EHVA) program will develop a Multidisciplinary Vaccine Platform (MVP) in the fields of prophylactic and therapeutic HIV vaccines. The Specific Objectives of the MVP are to build up: 1.Discovery Platform with the goal of generating novel vaccine candidates inducing potent neutralizing and non-neutralizing antibody responses and T-cell responses, 2. Immune Profiling Platform with the goal of ranking novel and existing (benchmark) vaccine candidates on the basis of the immune profile, 3. Data Management/Integration/Down-Selection Platform, with the goal of providing statistical tools for the analysis and interpretation of complex data and algorithms for the efficient selection of vaccines, and 4. Clinical Trials Platform with the goal of accelerating the clinical development of novel vaccines and the early prediction of vaccine failure. EHVA project has developed a global and innovative strategy which includes: a) the multidisciplinary expertise involving immunologists, virologists, structural biology experts, statisticians and computational scientists and clinicians; b) the most innovative technologies to profile immune response and virus reservoir; c) the access to large cohort studies bringing together top European clinical scientists/centres in the fields of prophylactic and therapeutic vaccines, d) the access to a panel of experimental HIV vaccines under clinical development that will be used as benchmark, and e) the liaison to a number of African leading scientists/programs which will foster the testing of future EHVA vaccines through EDCTP

By essence, diagnostic procedures intend to look for a certain panel of pathologies according to the risk factors or the symptoms of the patients to prevent further contaminations. This approach is particularly crucial in the context of concomitant epidemics affecting the same kind of populations such as HIV and Viral Hepatitis and Syphilis. Despite the huge effort made on HIV diagnostics, its main co-infections Viral Hepatitis and Syphilis has been widely ignored, particularly in SSA where less than 95% of infected people know their status (WHO 2021). Such underdiagnosis lead 4,5m new infections yearly over the world, and 1,8m deaths with at least 32% occurring in SSA. Those new infections in SSA are mainly due mother-to-child transmission, due to insufficient combined testing of pregnant women. The other cause is due to the present complexity of the testing algorithm to orient HBV pregnant women with active viremia toward treatment. A fully portable, autonomous multiplexed Point of Care device (3kg, 8h autonomy) has been developed. It is capable to perform 4 to 8 immuno-analyses in parallel in less than 15mn filing using 50µL of capillary blood. A first panel has been developed targeting HIV 1 & 2, Viral Hepatitis B and C. The goal of this project is first to evaluate the kit in SSA to see how the technology behave in different environments (Temperature, Humidity) and with blood presenting multiple other infections. MagIA IBC solution will be thus evaluated in lab and in the field among pregnant women to assess the performance and its impact on the Prevention of Mother To Child Transmission (PMTCT) particularly in region with low HIV prevalence where no testing is performed at all. Meanwhile a syphilis screening assay will be implemented and evaluated to better meet WHO Triple Elimination screening. ALAT and HBe-Ag assay will be developed to propose a Test and Treat approach for Hep B and further decrease mother to child transmission of Hepatitis B.

Tuberculosis (TB) remains a global health problem. The most lethal and disabling form of TB is tuberculous meningitis (TBM), with an estimated 100,000 new cases occurring per year. In sub-Saharan Africa, TBM mortality reaches 40% in HIV negative patients and up to 70% in HIV co-infected patients. Since decades, TBM treatment is based on a regimen used against pulmonary TB, which probably results in suboptimal drug levels in the cerebrospinal fluid (CSF). The main objective of INTENSE-TBM is to reduce the mortality and neurological complications of TBM in adults with or without HIV co-infection in sub-Saharan Africa (SSA). This is investigated via a multicentre randomised multicentre Phase III clinical trial involving 768 patients in four SSA countries to evaluate the efficacy of an intensified TB treatment regimen during the first two months of TB treatment, including high-dose rifampicin and linezolid (repurposed drug), with the addition of aspirin (not as yet authorized for TBM). This intensified TB treatment is expected to reduce mortality by at least 30% for each of the interventions and minimize neurological sequalae. The INTENSE-TBM trial is the largest ongoing trial in the field of TBM worldwide. If superiority of this experimental arm is demonstrated in terms of reduced mortality, it will become the first Phase III study to demonstrate survival benefit from intensified TBM treatment. As per the expected outcomes of this EDCTP-3 call, INTENSE-TBM-2, as the continuation of INTENSE-TBM, a clinical trial funded by EDCTP2 and whose activities were disrupted during the COVID-19 pandemic, aims at concluding the ongoing activities of the EDCTP-2 project. It also aims at complying with ethical issues, such as fully validating the willingness of trial participants to take part in the clinical investigations.

Ebola Virus Disease (EVD) outbreaks represent significant threats to public health and require effective countermeasures to minimize transmission and reduce mortality. The r-VSV-ZEBOV vaccine (Ervebo®) demonstrated efficacy in protecting contacts and contacts of contacts and has since been widely used in ring vaccination strategies in the Democratic Republic of Congo (DRC) outbreaks. However, its efficacy for high-risk contact is more and more debated. Furthermore, two monoclonal antibodies (mAbs), Ansuvimab (Ebanga®) and REGN-EB3 (Inmazeb®), have demonstrated their efficacy as treatment in reducing mortality in patients with EVD. With the availability of these management and prevention tools, the question of their use in Post-Exposure Prophylaxis (PEP), to protect individuals from contracting EVD after a high-risk contact, is more important than ever to effectively control EVD. The EBO-PEP consortium built on a highly successful collaboration between African and European institutions and NGOs. and allow to maintain a network for knowledge sharing and consortium collaboration to fight against EVD in Africa. The overall objective of the EBO-PEP project is to increase the portfolio of therapeutics tools against EVD, by evaluating a PEP strategy for high-risk contact. This will be accomplished through a multi-epidemic, multi-countries phase III clinical trial to test the efficacy of mAbs used as PEP during outbreak period. To address this objective, we focus our activities on 3 specific objectives: - to set up a multi-epidemic, multi-site and multi-countries phase III clinical trial in Africa to test the efficacy of mAbs used as PEP for EVD high-risk contact (EBO-PEP study), - to strengthen the capacities of clinical researchers and increase the knowledge and engagement of the community on EVD research, - to define the best PEP strategy for high-risk contact and to advocate for PEP implementation in the countries affected by EVD.

Lassa fever (LF) is an acute febrile illness associated with bleeding, organ failure, and shock caused by Lassa virus. LF causes outbreaks in West African with in-hospital mortality up to 12%. Challenges in the clinical care of patients are multiple due to the limited availability of LF molecular diagnostics, the risk for nosocomial transmission, and the limited treatment options.There are currently no safe and effective treatment options available for LF, except ribavirin, the efficacy of which is debated. The clinical development and accessibility of effective treatment options would be a game-changer towards reducing mortality associated with this disease and limiting its socio-economic impact. Nigeria is the country by far most affected by LF in the world with about 80% of global cases. The INTEGRATE consortium builds on a more than 15 years lasting highly successful collaboration between leading European and West African institutions focusing on the joint priority to better understand, manage, and combat LF in West Africa. The overall objective of the INTEGRATE project is to establish a GCP-compliant adaptive clinical platform trial in West Africa (Nigeria and other countries) to test the efficacy, tolerability and safety of repurposed and novel drug candidates for the treatment of LF. To address this objective, we focus our activities on 3 specific objectives: - to develop and implement an adaptive randomised controlled phase II-III clinical platform trial evaluating drugs with proven preclinical activity against LF. - to build capacity for sustainable and independently conducted clinical research in West Africa by developing site, laboratory and medical care capacity through North-South and South-South technology transfer and training. This activity encompasses capacity building of the lead Nigerian institution in GCP compliant clinical trial sponsorship. - to engage communities with the proposed work plan and to assess acceptability of the trial.