Work Packages
Work packages
WORK PACKAGE 1 - Controlled Human Malaria Infection Vaccine Trials in East Africa
The main objective of WP1 is to undertake clinical vaccine trials involving controlled human malaria infection (CHMI) in Kenya and Tanzania.
Clinical Trials
VAC074 - Safety, immunogenicity, and efficacy of R21/Matrix-M and ChAd63/MVA-ME-TRAP in the context of controlled human malaria infection: A Phase IIb Trial in Kenyan Clinicaltrials.gov link
This trial started in June 2022 in Kilifi, Kenya where we are testing two components of the multi-stage malaria vaccine; R21/Matrix-M (sporozoite stage) and ME-TRAP (liver stage) in a human malaria challenge (CHMI).
VAC080 - A Phase Ib clinical trial to assess the safety and immunogenicity of the blood-stage Plasmodium falciparum malaria vaccine candidate RH5.1/Matrix-M in healthy adults and infants in Tanzania Clinicaltrials.gov link
This trial started in January 2021 where we are testing the safety and immune response of the blood stage malaria vaccine component, RH5.1/Matrix-M in Bagamoyo, Tanzania. The trial was fully enrolled by April 2021 and the vaccine was well tolerated by adults and children. Immunology analysis of samples is currently underway.
VAC083 - A pilot study to assess the safety and feasibility of controlled blood-stage Plasmodium falciparum human malaria infection through experimental inoculation of cryopreserved infected erythrocytes in healthy adults with varying degrees of prior exposure to malaria Clinicaltrials.gov link
We are establishing a blood stage malaria challenge model in the IHI facility in Tanzania which will allow us to test the efficacy of the blood-stage malaria vaccine component more accurately in people who live in a malaria endemic area. The first blood-stage malaria CHMI took place successfully in July 2022.
WORK PACKAGE 2 - Age de-escalation phase I trials in Kenya and in The Gambia
The main objective of WP2 is to undertake age de-escalation phase I trials in Kenya and The Gambia.
Clinical Trials
VAC073 - A Phase 1b, open-label, age de-escalation, dose-escalation study to evaluate the safety and immunogenicity of different doses of a candidate malaria vaccine; adjuvanted R21(R21/MM) in adults, young children and infants in Kilifi, Kenya Clinicaltrials.gov link
This trial started in April 2019 where we are testing the safety and immune response of the sporozoite stage of the multi-stage malaria vaccine, R21/Matrix-M in healthy adults, children and infants in Kilifi, Kenya. The trial is now complete with the last volunteer last visit occurring in June 2022. The vaccine was safe in all age groups and elicited a strong immune response which was successfully boosted after a year post primary series.
VAC086 - A Phase Ib multi-stage Plasmodium falciparum malaria vaccine study to assess the safety and immunogenicity of the blood-stage vaccine candidate RH5.2 virus-like particle (VLP) in Matrix-M and the pre-erythrocytic stage vaccine candidate R21 in Matrix-M, both alone and in combination, in adults and infants in the Gambia Clinicaltrials.gov link
This is a multi-stage malaria vaccine trial planned to start in Q4 of 2022 to test both the sporozoite stage vaccine R21/Matrix-M and the blood-stage vaccine RH5.1/Matrix-M in both adults and infants in the Gambia.
WORK PACKAGE 3 - Phase IIb vaccine efficacy trial against clinical malaria in infants
The main objective of WP3 is to undertake a large multi-stage malaria vaccine phase II efficacy trial in 400 infants (5-9 months of age) in 3 African countries; Kenya, Sierra Leone and Burkina Faso
Clinical Trials
VAC076 - A Phase Ib/IIb randomised controlled trial of the safety, immunogenicity and efficacy of a candidate malaria vaccine, R21 adjuvanted with Matrix-M (R21/MM), in 5-17 month old children in Nanoro, Burkina Faso Clinicaltrials.gov link
We progressed R21/Matrix-M in a larger randomised controlled clinical trial in 450 children in Nanoro, Burkina Faso. We collected safety and immunogenicity data as well as determined how effective the vaccine is in preventing malaria. The vaccine was safe and induced very potent antibody responses in these 5-17 month olds. Excitingly, the vaccine trial showed important high level efficacy of 77% in preventing episodes of clinical malaria in the R21/Matrix-M vaccinated groups compared to the control group over 12 months of follow-up. A booster vaccine given after one year later stimulated as high immune responses as were seen following the primary series of vaccinations. The results of this trial were published recently in the Lancet. As a results of this successful booster dose we went on to boost the infants a second time. The results of this additional booster will be published shortly.
VAC091 is a Phase IIb randomised controlled trial of the safety, immunogenicity and efficacy of the blood-stage malaria vaccine candidates RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in infants aged 5-17 months in Burkina Faso. Clinicaltrials.gov link
VAC087 will assess malaria vaccines R78C, RH5.1 and R21 as standalone multi-stage vaccines for efficacy in a Phase 2b trial in Burkina Faso. R78C is a soluble RIPR EGF-CyRPA fusion protein vaccine, which shows promising pre-clinical data and clinical data in a Phase 1a trial in healthy UK adults.
VAC093 is a Phase 1b age de-escalation, dose-escalation, open-label safety and immunogenicity trial of the multi-stage malaria vaccine candidate R21 + RH5.1 + R78C with Matrix-M in adults and children aged 5-17 months in Burkina Faso. The triple combination of RH5.1/R78C/R21 is a first-in-human Phase 1b trial to assess safety and reactogenicity and to optimise the dose of the combination prior to taking it forward to a Phase 2b trial.
WORK PACKAGE 4 - Transmission-blocking vaccine trials
The main objectives of WP4 are to identify Burkinabe villages with high malaria transmission rates then to undertake a large malaria vaccine phase IIb efficacy trial using the transmission blocking vaccine, Pfs25-IMX313 in children, and finally, to test the impact of this vaccine on mosquito-to-human transmission in Kilifi, Kenya.
Surveillance work
To prepare for later mosquito-stage vaccine trials, large surveys took place in Bobo-Dioulasso, Burkina Faso to determine where the highest rates of malaria transmission occur. 30,000 mosquitoes were collected and dissected. Parasite surveys also took place where monthly blood samples were taken from 100 children and the parasites quantified. As a result of these surveys and analyses, and with respect to the transmission index, accessibility and health facilities, three villages have been identified as possible locations for the later IIb transmission blocking trial. In parallel we are optimising laboratory tests where mosquitoes are fed potentially infectious blood samples in order to assess the infectivity of the study participants in future trials.
Clinical Trials
VAC082 - A phase Ib age de-escalation and dose escalation open label clinical trial of the safety, immunogenicity and ex vivo efficacy of a candidate malaria vaccine Pfs25-IMX313/Matrix-M administered intramuscularly in healthy adults and young children in Tanzania Clinicaltrials.gov link
This trial started in April 2021 where we are testing the transmission blocking candidate component of the multi-stage malaria vaccine, Pfs25-IMX313/Matrix-M in adults and young children in Bagamoyo in Tanzania. The vaccine has a good safety profile in both adults and children. Immunoassays are on-going. The trial is due to be complete in 2023.
Due to the exciting results from a Phase 1a Pfs48/45 transmission-blocking trial in Oxford, UK we are in the position of having two equally promising transmission-blocking vaccine candidates (including Pfs25-IMX313 tested at Phase 1b in VAC082). VAC099 is a Phase 1b open-label clinical trial of the safety, immunogenicity and ex vivo efficacy of two candidate malaria-transmission blocking vaccines, Pfs25-IMX313 and Pfs45/48 in Matrix-MTM adjuvant administered alone and in combination to adolescents, young children and adults in Burkina Faso. This trial will compare the two vaccine candidates and it will test for any synergistic effect.
WORK PACKAGE 5 - Capacity-building and Networking
The main objectives of WP5 are to undertake capacity building and to facilitate networking between consortium partners as well as support African students in short and long term training programmes
During the MMVC project, we also aim to undertake capacity building and to help networking between consortium partners, as well as support African students in training programmes. Capacity building is taking place in IRSS-DRO, Burkina Faso where a new research facility is being developed to perform large scale laboratory analysis of blood samples. Capacity building is also taking place in IHI, Bagamoyo to establish the blood-stage challenge model.
The consortium has appointed three PhD students and two MSc student who are undergoing training and analysing samples for their projects. As of November 2024, all five students supported by MMVC programme have completed their studies.
WORK PACKAGE 6 - Management and Sponsorship
The main objectives of WP6 is to set up an appropriate and effective project management framework for the project.
The University of Oxford sponsors all of the clinical trials in the MMVC. The MMVC project management groups, the steering committee and data safety monitoring committees continue to contribute at regular meetings and ensure the successful progress of the programme.
The Covid-19 pandemic presented many challenges in conducting medical research, however the MMVC consortium continued to make good progress while minimising risk to trial participants and consortium members.