This trial will evaluate whether relatively non-immune populations in endemic countries can effectively generate significant cellular and humoral immune responses that confer protection against P. falciparum infection after inoculation of aseptic, purified, vialed, metabolically active, non-replicating (live, radiation attenuated) Plasmodium falciparum sporozoites (PfSPZ Vaccine) administered intravenously (IV).
This is a single center, Phase 1, dose escalating, randomized, double blind, controlled trial. Seventy-three healthy male volunteers, aged 18 to 35 years will be recruited. The study will have 5 study groups that will include 49 volunteers who will be intravenously injected with PfSPZ Vaccine, 8 control volunteers who will receive normal saline and 16 additional control volunteers who will be recruited at the time of controlled human malaria infection (CHMI) at 3 and 24 weeks. The control volunteers will help better assess the occurrence of AEs compared to background disease patterns that occur in this tropical area, and the performance of the vaccine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
67
Aseptic, purified, vialed, metabolically active, non-replicating (live, radiation attenuated) cryopreserved Plasmodium falciparum sporozoites (PfSPZ)
Live, infectious, aseptic, purified, vialed, cryopreserved Plasmodium falciparum sporozoites (PfSPZ) for CHMI
Bagamoyo Research and Training Center, Ifakara Health Institute, Kingani Estate, PO Box 74
Bagamoyo, Tanzania
Safety and tolerability endpoints
* Solicited local (IV site) and systemic AEs (AEs) observed in the 7 days after each vaccination and each CHMI. * Unsolicited AEs observed after the first vaccination until day 28 after the last vaccination for volunteers who do not undergo CHMI#1 (e.g. Group 1, those who do not complete the CHMI portion in Groups 2 and 3, and volunteers in Group 4). * Unsolicited AEs observed after the first vaccination until day 28 after the CHMI#1 for volunteers who undergo CHMI#1 3 weeks after the last vaccination (e.g. Groups 2 and 3). * Unsolicited AEs observed from day CHMI#2 (which occurs 24 weeks after the last vaccination) until day 28 after CHMI#2 (e.g. Groups 2-5).
Time frame: Vaccination to CHMI (or 28 days after last vaccination); CHMI to 28 days after CHMI
Protective Efficacy after CHMI with PfSPZ Challenge (NF54) - CHMI Endpoints
Number of volunteers that remain parasite negative in each group through day 28 of follow up after CHMI with PfSPZ Challenge (NF54) IV inoculation. Three weeks after their last immunization, volunteers in Groups 2 and 3 will under go their first CHMI with 3.2 x 10\^3 PfSPZ Challenge (NF54) administered IV. Twenty-four weeks after the last immunization, volunteers from Groups 2 and 3 who underwent the first CHMI and did not become infected will have a second CHMI by IV injection of 3.2x10\^3 PfSPZ Challenge (NF54). Volunteers in Groups 4 and 5 will only participate in the second CHMI assessment. After CHMI, volunteers will be followed for evidence of infection with blood smears for 28 days.
Time frame: CHMI to 28 days after CHMI
Immune Responses after PfSPZ Vaccine
Cellular and humoral immune responses will be assessed in the vaccinated volunteers and controls (including central and effector memory responses and breadth and specificity of malaria antibodies).
Time frame: 16 months
Protective effect of the high dose PfSPZ Vaccine regimen
Number of volunteers negative in Group 3 and Group 4 compared to Group 2 through day 28 of follow up after homologous PfSPZ Challenge (NF54) IV inoculation.
Time frame: CHMI to day 28 after CHMI
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