The study is a single center, varied dose, open label study. A maximum of eighteen volunteers will be exposed to live NF54 P. falciparum sporozoites (PfSPZ Challenge) by intradermal injection. Volunteers will be divided into three groups of 6 volunteers, each group spaced 25 days apart (21 days after the last challenge of the last volunteer from the previous dose group).
In every group on day 1, two volunteers will be injected. On day 3 the remaining four volunteers of the group will be injected. Injections in subsequent volunteers are always spaced at least one hour apart in any group. Injection of subsequent (groups of) volunteers will only commence if the previous injection was shown to be safe. Three different doses of PfSPZ will be administered: a dose of 2,500 PfSPZ Challenge (Group 1); a dose of 10,000 PfSPZ Challenge (Group 2) if not all volunteers become thick smear positive (TS+) in Group 1; and a dose of 25,000 PfSPZ Challenge (Group 3) if there is not 100% TS+ in Group 2. If all volunteers in Group 1 (2,500 PfSPZ Challenge) become thick smear positive, then Group 2a will receive 1,000 PfSPZ Challenge. If all volunteers in Group 2a become TS+, the volunteers in Group 3a will receive 500 PfSPZ Challenge. If all volunteers in Group 2 (10,000 PfSPZ Challenge) become TS+, Group 3b will receive 5,000 PfSPZ. If less than 100% of volunteers in Group 2a (1,000 PfSPZ Challenge) become TS+ then Group 3c will receive 1,750 PfSPZ Challenge. The clinical, biological, parasitological and immunological data of these groups' volunteers will be compared. Volunteers and the investigator will not be blinded, but the laboratory personnel will be blinded.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Masking
NONE
Enrollment
18
each volunteer to receive a single dose
Radboud University Nijmegen Medical Center
Nijmegen, Netherlands
Number of volunteers with Plasmodium falciparum Infection
To achieve a 100% infection rate of human volunteers by intradermal injection of aseptic, purified, cryopreserved Pf sporozoites (PfSPZ Challenge)as measured by 100% thick smear positivity (thick blood smears) of all volunteers from one group
Time frame: Upto 7 months
Kinetics of infection
To compare parasite kinetics between different doses of intradermal injection of PfSPZ Challenge as measured by: * A significant difference in time of thick smear positivity between the groups of volunteers * A significant quantitative difference in parasitemia as measured by retrospective PCR between the groups of volunteers * A significant difference in kinetics of parasitemia between the groups of volunteers as measured by retrospective PCR * A difference in occurrence or intensity of signs or symptoms between the groups of volunteers
Time frame: Upto 7 months
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