The primary objectives of this study are to assess the safety and feasibility of blood-stage controlled human P. vivax malaria infection (CHMI) in healthy adult Thai volunteers through experimental injection of cryopreserved P. vivax infected erythrocytes, and to choose the optimal inoculation dose for future P. vivax CHMI studies. In this study, blood-stage CHMI will be conducted in 8 volunteers per inoculum stock who will each be infected with P. vivax by experimental injection with cryopreserved P. vivax infected erythrocytes, which were collected from the controlled human Plasmodium vivax malaria infection model through experimental sporozoite infection in Thai adults (NCT04083508) . There are currently 4 stocks of inocula from 6 volunteers in the NCT04083508 study, which have differing quantities and stages of parasites.
The total number of volunteers of this study will be up to 48 (8 volunteers per inocula stock). The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases, and will be treated according to the Research Proposal.
This study is funded by the UK Wellcome Trust. The grant reference number are Oxford/MORU: 212336/Z/18/Z and 212336/Z/18/A, and Mahidol University: 212336/A/18/Z and 212336/A/18/A.
Healthy Thai adult aged 20 to 55 years with weight at least 50 kg.
Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
Women only: Must practice continuous effective contraception for the duration of study period until 3 months post-challenge.
COVID-19 vaccination at least two doses of COVID-19 vaccines approved by WHO.
Positive malaria qPCR OR malaria film
Presence of any medical condition (either physical or psychological) which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
Presence of chronic disease or chronically use of medication
Use of systemic antibiotics with known antimalarial activity in the 30 days before challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
Parallel
An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum
Biological/VaccineAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with whole dose blood-stage inoculum (neat)
An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum
Biological/VaccineAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:5 dilution blood-stage inoculum
An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum
Biological/VaccineAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:10 dilution blood-stage inoculum
An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculum
Biological/VaccineAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:20 dilution blood-stage inoculum
Incident of treatment-emergent adverse events of blood-stage controlled human P. vivax malaria infection
Measured by (serious) adverse event (AE) occurrences
Choosing the optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration.
The optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration
Feasibility of primary P. vivax blood-stage CHMI, as measured by successful infection (development of detectable persistent parasitaemia by thick blood film +/- clinical symptoms)
Geometric mean and standard deviation/error of Pvs25 gene transcript copy number/microL at each time point
Measured by qPCR in experimental P. vivax infection through blood-stage challenge
Transmissibility of gametocytes from the infected volunteer to Anopheles mosquito vector
Measured by gametocytes from the infected volunteer to Anopheles mosquito vector using Membrane feeding assay
Cellular Immune response to primary P. vivax infection (frequencies, percentages (%), and expression level of mononuclear cells)
Immune cells including Innate and adaptive immune cells react and express during the PV infection (profile and frequency)
Level of antibodies and cytokines responses to primary P. vivax infection during different phase of infection
Immune cells defense PV antigen by determining the level of antibody response and inflammatory cytokine
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University of Oxford
Lead sponsor
Wellcome Trust
Collaborator
