Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for repeat CHMI. A total of 30 adult, healthy, malaria naïve volunteers will receive three injections by Direct Venous Inoculation (DVI) of either placebo (n = 10), 51,200 PfSPZ Challenge (NF54) (n = 10), or 150,000 PfSPZ Challenge (NF54) (n = 10) under chemoprophylaxis with A/P at 4 week intervals. The placebo will be normal saline (0.9% NaCl). Ten weeks after the last dose of PfSPZ Challenge (NF54) for immunization, volunteers will undergo first CHMI and followed until asexual blood stage parasitemia, detected by quantitative real time PCR (qPCR) or thick blood smear microscopy. If parasitemic, they will be treated with A/P (used in this case as a standard treatment regimen). In the event of no parasitemia, volunteers will be followed until Day 28 post-CHMI and will not receive A/P. Sixteen to forty-four weeks after the last immunization, a second CHMI will be administered to assess longevity and cross-strain protection. All volunteers will be followed up to 28 days post-inoculation. Those developing parasitemia will be treated with A/P. Volunteers of Group A will have CHMI with PfSPZ Challenge (NF54) followed by PfSPZ Challenge (7G8). Volunteers of Group B will have CHMI with PfSPZ Challenge (NF54) or PfSPZ Challenge (7G8) followed by PfSPZ Challenge (7G8). In the case that protective efficacy in Group A is ≥75% CHMI sequence will be 7G8-7G8. In the case that protective efficacy against homologous Challenge in Group A is \<75%, volunteers will receive the same sequence as in Group A (NF54-7G8).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
30
Combination drug for chemo-prophylaxis or treatment of malaria
cryo-preserved Plasmodium falciparum sporozoites injected by venous inoculation
0.9% NaCl solution for injection
Number or occurrence of related Grade 3 and 4 adverse events (AEs) and serious adverse events (SAEs)
Time frame: from time of first administration of A/P until the last follow up visit, 414 days after first administration
Occurrence of any related AE
Time frame: from time of first administration of A/P until the last follow up visit, 414 days after first administration
Proportion of protected volunteers
. Protection is defined as the absence of parasites in the peripheral blood for 28 days following first and second CHMI with PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) in volunteers receiving PfSPZ-CVac with A/P. Parasitemia is defined as at least one qPCR result above 100 parasites per mL among three positive results at least 12 hours apart or as a positive thick blood smear. Statistical testing is hierarchical: 1) protection against first CHMI, 2) protection against second CHMI.
Time frame: From time of PfSPZ challenge administration until 28 days after PfSPZ challenge
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