A highly effective malaria vaccine against Plasmodium falciparum should help prevent half a million deaths from malaria each year. New vaccine technologies and antigen discovery approaches now make accelerated design and development of a highly effective multi-antigen multi-stage subunit vaccine feasible. Leading malariologists, vaccine researchers and product developers will here collaborate in an exciting programme of antigen discovery science linked to rapid clinical development of new vaccine candidates. Our approach tackles the toughest problems in malaria vaccine design: choice of the best antigens, attaining high immunogenicity, avoiding polymorphic antigens and increasing the durability of vaccine immunogenicity and efficacy. We take advantage of several recent advances in vaccinology and adopt some very new technologies: sequencing malaria peptides eluted from the HLA molecules, parasites expressing multiple transgenes, multi-antigen virus-like particles constructed with new bonding technologies, delayed release microcapsules, and liver-targeted immunisation with vaccine vectors. We enhance our chances of success by using a multi-stage multi-antigen approach, by optimising the magnitude and durability of well-characterised immune responses to key antigens, and using stringent infectious challenges and functional assays as established criteria for progression at each stage. The consortium comprises many of the foremost researchers in this field in Europe with leading groups in the USA, Australia and Africa. We link to EDCTP programmes and harmonise our timeline to fit with the recent roadmaps for malaria vaccine development. We include a major pharma partner and several excellent European biotech companies helping enhance Europe’s leading position in the commercial development of vaccines. This ambitious and exciting programme should have a high chance of success in tackling the major global health problem posed by malaria.

Natural epidemics and outbreaks of emerging viral epidemics are growing problems internationally. The general aim of the CCHFVaccine project is to develop and deliver a vaccine, which can significantly increase our capacity to control the situation of Crimean Congo Haemorrhagic fever (CCHF) disease on a global basis. The proposed work program on CCHF virus aims to build a multidisciplinary research network, able to deliver vaccine candidates, methods and procedures eligible for clinical trials, with a special focus on prevention. Thanks to the background, unique facilities and tools available among the consortium participants, CCHFVaccine will deliver tools for countering the threat of this infection in Europe and endemic areas of the world. This work program will attempt to fill gaps in CCHFV virus research on immunology and vaccinology. To achieve this overall aim, an intensive work plan will be put in place with the following specific objectives: i) to produce vaccine candidates, ii) to bring several unique animal models into front line vaccine research, iii) to validate and bring the most promising vaccine candidates to clinical trials, iv) to ensure that an immune mediated protection is adequately understood, v) to perform clinical trials at Phase I and ensure a strategy for the effective deployment and utilization in resource-poor countries, and vi) to link this project to public health bodies, NGOs and vaccine companies. The proposed CCHFVaccine project will succeed in bringing together selected competitive advantages such as: operating capacity with appropriate facilities (state-of-the-art BSL-4s) and the only animal BSL-4 -with capacity to challenge domestic animals in Europe, highly experienced researchers in the development and evaluation of vaccine candidates, authorities and entities of human and animal health, clinical samples from endemic countries, and an international network proven to be functional by the previous EU-funded CCHFever and EDENext.

Plasmodium vivax is the most widespread malaria and constitutes a significant proportion of human malaria cases. P. vivax accounts for 100-400 million clinical cases each year among the 2.5 billion people living at risk in Latin America, Oceania and Asia. The recently revised Malaria Vaccine Technology Roadmap to 2030 recognises the severity of P. vivax malaria and calls for a vaccine intervention to achieve 75% efficacy over two years – equally weighted with P. falciparum. However, despite this global health need, efforts to develop interventions against this parasite have lagged far behind those for P. falciparum, in large part because of critical bottlenecks in the vaccine development process. These include i) lack of assays to prioritise and down-select new vaccines due to lack of an in vitro P. vivax long-term culture system, and ii) lack of easy access to a safe controlled human malaria infection (CHMI) model to provide an early indication of vaccine efficacy in humans. The Objectives of this MultiViVax proposal will address these critical bottlenecks and shift the “risk curve” in order to better select successful vaccine candidates against multiple lifecycle stages of P. vivax: 1. We will establish a P. vivax CHMI model in Europe for the first time to facilitate the better selection of effective vaccines and remove the current bottleneck for their early-phase clinical testing. 2. We will utilise this CHMI model to identify novel antigens associated with protective blood-stage immunity in humans by taking advantage of recent advances in immuno-screening and parasite RNASeq. 3. We will progress existing vaccines targeting the current leading antigens for both the blood- and transmission-stages along the clinical development pipeline. 4. We will develop novel transgenic parasites for use in assays in order to overcome the current bottleneck in vaccine down-selection caused by the inability to culture P. vivax parasites.