The 2nd Generation Malaria Vaccine Consortium (MVC-2G) will build on the programmatic use of the first-generation Plasmodium falciparum vaccine, R21 with Matrix-M™, and accelerate the clinical development of the leading second-generation multi-stage P. falciparum malaria vaccine comprising R21 and two novel blood-stage components, RH5.1 and R78C, all formulated in Matrix-M™. It will achieve this through a multi-disciplinary workplan, underpinned by international cooperation, that will accelerate the future achievement of the United Nations’ Sustainable Development Goal 3 (SDG3) in sub-Saharan African countries. Its specific objectives are to: 1. Demonstrate safety and superior efficacy against clinical malaria (over R21/MM alone) of the leading second-generation multi-stage vaccine candidate R21+RH5.1+R78C/MM in a Phase 2b trial in 5-17 month old African infants, in a seasonal setting; 2. In parallel, undertake Phase 1b assessment of the second-generation multi-stage vaccine in African infants to define a 3 or 4 dose delivery schedule that is better aligned with EPI and end-user community expectations, aiming for lower cost of goods and to facilitate improved future uptake of a second-generation product; 3. Demonstrate safety and superior efficacy of the multi-stage vaccine (over R21/MM alone) delivered in an optimised age-based schedule in a multi-site Phase 2b trial in African infants in seasonal and perennial settings; 4. Generate evidence to support use of the multi-stage vaccine in future malaria elimination campaigns by assessment of i) efficacy in adults by CHMI, and ii) safety and immunogenicity in older children; 5. Support the next-generation of early-career African scientists, across all partners in the Consortium, by growing a South-South network to facilitate hands on clinical and laboratory training; and 6. Undertake early engagement with regulators in partner countries to facilitate translation and future registration of this multi-stage vaccine.