A highly effective malaria vaccine is a major goal of global health research and will likely require a multi-stage product. MultiMalVax will develop a highly effective multi-stage malaria vaccine to the point of proof-of-concept phase II testing in Europe, prior to trials in malaria-endemic areas.Remarkable recent advances in vaccine design for all four stages of the P. falciparum parasite’s life-cycle allow testing of a multi-stage multi-component vaccine for the first time, with strong chances of success. These advances are i) the availability of a new vectored prime-boost vaccination regime based on the ReiThera Srl's chimpanzee adenovirus technology that has been found to induce exceptionally potent CD8+ T cell responses and high titre antibodies against multiple malaria antigens; ii) the development of an improved version of the leading partially protective RTS,S sporozoite vaccine candidate, termed R21, that lacks the excess of HBsAg in RTS,S; iii) the identification, using a vector technology screen, of the blood-stage antigen RH5 as the first antigen to induce potent strain-transcending neutralisation of blood-stage parasites in in vitro growth inhibition assays; and iv) the demonstration that vector-induced antibodies against two mosquito-stage antigens can induce 100% transmission blocking against field isolates of P. falciparum in Africa.We will undertake four phase I / II clinical trials to assess the pre-erythrocytic, blood-stage and mosquito-stage components individually, and then together, using state-of-the art immunomonitoring, key functional assays of vaccine-induced immunogenicity, and sporozoite and blood-stage parasite challenges to measure efficacy prior to field testing. This SME-led collaboration of a leading SME, two universities, the major European product development partnership for malaria vaccines, and a global pharmaceutical company will provide complementary abilities to accelerate development of this promising product.