Heartwater, caused by Ehrlichia ruminantium (ER) , constitute a major threat to ruminant production in Africa, affecting mainly small ruminants. Although a commercial vaccine is available, it presents so many drawbacks that its use is limited. An efficient, cost-effective and safe vaccine against heartwater to alleviate poverty of smallholder farmers and contribute to a sustainable agriculture in Africa is needed. The inactivated vaccine constitutes the most advanced experimental vaccine against heartwater. The main drawback of any experimental vaccine is the high antigenic diversity of ER strains, limiting its efficacy under field conditions. Our consortium composed of 2 European and 4 African partners propose to tackle this limitation by including a cocktail of strains of different regional genotypes newly isolated within the project. First, the genetic diversity of ER strains from Benin, Burkina Faso, Niger and South Africa, will be assessed during the first two years of the project allowing a follow-up and identification of predominant strain variations circulating over time. New ER strains from different genotypes will be isolated and included in two regional multivalent vaccines. Finally, the efficacy of the inactivated vaccine will be evaluated in field conditions, tested in Burkina Faso and South Africa, respectively, with a new promising oil adjuvant and with a single injection and protection-associated biomarkers will be identify to minimize the need for challenges after any new vaccine trials. Process of production of improved vaccine formulations at industrial level and efficient quality controls will be available at the end of the project. Current project will also allow increasing regional heartwater diagnostic and research capacities. Special efforts will be done to share the research products with stakeholders and end-users such as farmers and local manufacturers.