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 to assist efforts towards malaria elimination.  In this project we are developing the first multi-stage vaccine for malaria designed to target all 4 stages of the P. falciparum parasite’s life-cycle; sporozoite stage, liver stage, blood stage and mosquito stage.  We will then test these vaccines in clinical trials in Africa. Firstly we will test each component of the multi-stage malaria vaccine to ensure the vaccines are safe, stimulate an immune response in the body, and in some of our studies, are effective against malaria. Two of the component vaccines called R21/Matrix-M which targets the ‘sporozoite’ stage of the malaria life-cycle and ME-TRAP which targets the ‘liver’ stage of the life-cycle are being tested in a clinical trial in Kilifi, Kenya.  We will vaccinate healthy adult volunteers, then introduce sporozoites into healthy volunteers and test whether these adults develop malaria.  We have received the required ethical approval to proceed with this trial from both the Kenyan and UK ethical committees and is due to start in November 2019. Our aim is to develop vaccines for all ages of Africans at risk of malaria which includes young infants.  In order to do this, we must first show that the vaccines are safe and effective in adults, then children then young children/infants.  We are currently testing the R21/Matrix-M vaccine in a clinical trial in Kilifi, Kenya in adults and children aged from 1-5 years, down to infants aged 5-12 months.  Once all of the required approvals were in place, the local population was informed about the trial and volunteers came forward to take part in the trial.  The results from this trial so far have been very encouraging, and no safety concerns have been raised.  An independent body made up of medical experts (called the DSMB) review the trial data at regular intervals to check the trial can proceed.  All of the vaccinations in the trial are expected to be complete by September 2019. Once we have shown that the individual components of the proposed multi-stage malaria vaccine perform well, we plan to undertake a large clinical trial (phase IIb) in infants in several African countries combining some or all of the vaccines.  This trial is not due to start until late in 2020.  In order to progress this work more rapidly, we have introduced a new randomised controlled trial into the programme to test the R21/Matrix-M vaccine in 450 infants aged 5-17 months in Nanoro, Burkina Faso.  We plan to test how safe, how immunogenic and how effective this vaccine is by vaccinating the infants before the malaria season starts, then collecting how many infants develop malaria during the malaria season.  This trial has progressed exceptionally quickly.  After all the required approvals were in place, and the local community were sensitized, all 450 infants were vaccinated by June 2019.  The vaccines have been very well tolerated by the infants, and no safety concerns have arisen.  After reviewing safety data, the DSMB recommended that the trial proceed.  We will collect the incidences of malaria in the infants during the second half of 2019, and will have preliminary results for the first field trial to test the efficacy of R21/Matrix-M by early 2020. We hope that this rapid progression into field trials of R21/Matrix-M safely will progress the multi-vaccine stage of the project even more quickly to allow licensure of a safe, effective, affordable malaria vaccine to be available to every African. Vaccines to target the ‘blood’ and ‘mosquito’ stages of the malaria life-cycle are being manufactured and will be tested in clinical trials in January 2020.  To prepare for the mosquito stage trials, surveys are taking place in Bobo-Dioulasso to determine where the highest rates of malaria transmission take place, and the laboratory tests which will be used in the trial are being developed. We will then test the efficacy of the vaccine by ‘challenging’ the vaccinated Tanzanian adult volunteers by injecting malaria infected blood into them and observing whether these volunteers develop malaria. During this large malaria vaccine project, we also aim to undertake capacity building and to help networking between consortium partners, as well as support African students in training programmes.  During this period, capacity building is taking place in IRSS, Bobo-Dioulasso where a new research facility is being developed to perform large scale laboratory analysis of blood samples which will result from the clinical trials to test the mosquito stage vaccine. The consortium has selected the PhD students to take part in research projects within MMVC.  Three African students have been selected from 103 applicants, and their project titles and institutions have been finalised. We have also set up an appropriate and effective project management framework for the project with both a project steering committee and data safety monitoring committee.  The consortium met at a successful project kick-off meeting in Dakar, Senegal in April 2018. In summary, the MMVC is a well-managed consortium which is making good progress to meet the objectives in period 1. More information can be found about the project by visiting our website; https://www.jenner.ac.uk/mmvc
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 Association Epicentre Partner France
3 European Vaccine Initiative Partner Germany
5 Groupe de Recherche Action en Santé sarl. Partner Burkina Faso
6 Ifakara Health Institute Trust Partner Tanzania
7 Institut de Recherche en Science de la Santé– Direction Regional de l’Ouest Partner Burkina Faso
9 Institut de Recherche en Science de la Santé-Unité de Recherche Clinique de Nanoro Partner Burkina Faso
10 Institut de Recherche pour le Développement Partner France
11 Janssen Vaccines & Prevention B.V. Partner Netherlands
12 London School of Hygiene and Tropical Medicine Partner United Kingdom
14 Novavax AB Partner Sweden
15 Serum Institute of India Pvt. Ltd. Partner India
16 University of Sierra Leone Partner Sierra Leone