Project: Multi-Stage Malaria Vaccine Consortium: field efficacy testing of a malaria vaccine targeting all four stages of the parasite's life-cycle

Acronym MMVC (Reference Number: RIA2016V-1649)
Duration 01/04/2018 - 30/09/2023
Project Topic A high-efficacy malaria vaccine is urgently required to reduce the unacceptable burden of malaria mortality and morbidity in Africa and to assist efforts towards malaria elimination. An ideal malaria vaccine would target all stages of the parasite’s life-cycle but no such vaccine has reached clinical trials in Africa. We propose here to develop a very promising multi-stage vaccine which will progress to a large phase IIb efficacy trial in West and East African 5-9 month olds. All four potential components of the vaccine have strong validation. The anti-sporozoite vaccine component, R21, is a next-generation RTS,S vaccine with a simpler but equally potent adjuvant, matrix-M. This recently showed 82% sterile efficacy in a UK phase II sporozoite challenge trial using just 10 micrograms of R21 per dose (one fifth of the standard RTS,S dose). The liver-stage vaccine employs adenoviral and MVA vectors that showed good safety and high efficacy in EDCTP-supported African trials.The blood-stage component is the leading conserved PfRH5 antigen that induces high-titre cross-strain neutralising antibodies in phase I trials. The sexual-stage antigen is the conserved Pfs25, multimerised as a nanoparticle thereby enhancing antibody immunogenicity. We will undertake a tightly co-ordinated series of lead-in trials in 2018-2020 building towards a phase IIb efficacy trial in 5-9 month olds from late 2020 to2023. We will first evaluate in East Africa the efficacy of the vaccine and selected components in controlled human malaria infection trials, availing of this new capacity in Kenya and Tanzania. We will undertake age de-escalation trials of both the R21 component and the combination vaccine documenting safety and immunogenicity, and identifying a preferred deployable immunisation regime, at likely 6, 7 and 9 months of age with a delayed booster. This will lead to a phase IIb trial in infants at sites of differing malaria endemicity in Kenya, Sierra Leone and Burkina Faso. We will measure primarily impact on malaria clinical episodes aiming to meet or exceed the WHO Roadmap target of 75% efficacy. In parallel we will build new capacity to test the ability of the combination vaccine and/or its transmission-blocking component to block human-to-mosquito transmission in African adults, foreseeing the potential use of the combination vaccine in elimination campaigns. This consortium, comprising very experienced and new African trial sites with leading northern institutions and companies, offers an unprecedented opportunity for rapid development of a deployable high-efficacy multi-stage malaria vaccine.
Network EDCTP2
Call Vaccines for poverty-related diseases (PRDs)

Project partner

Number Name Role Country
1 The Chancellor, the Masters and the Scholars of the University of Oxford Coordinator United Kingdom
2 European Vaccine Initiative Partner Germany
3 Institut de Recherche en Science de la Santé-Unité de Recherche Clinique de Nanoro Partner Burkina Faso
4 Institut de Recherche en Science de la Santé– Direction Regional de l’Ouest Partner Burkina Faso
5 Ifakara Health Institute Trust Partner Tanzania, United Republic of
6 University of Sierra Leone Partner Sierra Leone
7 Institut de Recherche pour le Développement Partner France
8 Groupe de Recherche Action en Santé sarl Partner Burkina Faso
9 London School of Hygiene and Tropical Medicine Partner United Kingdom
10 Novavax AB Partner Sweden
11 Janssen Vaccines & Prevention B.V. Partner Netherlands, The
12 Epicentre Partner France
13 Serum Institute of India Pvt. Ltd. Partner India