Regimen Optimization Trial of PfSPZ Vaccine in Equatorial Guinea

This double‐blind, placebo‐controlled clinical trial will be conducted in 104 Equatoguinean healthy men and women 18‐45 years of age divided into four groups of 26 subjects receiving one of four dosing regimens. The study is designed to test the hypothesis that 2 or 4 doses of 9x10^5 PfSPZ of PfSPZ Vaccine administered by direct venous inoculation (DVI) over 6‐7 days as the priming immunization, with or without a boosting immunization at 4 or 16 weeks after the last priming dose, will (1) be safe and well tolerated; and (2) induce immunity leading to protection against homologous controlled human malaria infection (CHMI) performed at 8 weeks after the final immunization by DVI injection of PfSPZ Challenge. The first regimen will test the radiation‐attenuated whole sporozoite PfSPZ Vaccine in a dose of 9.0x10^5 administered by DVI with four priming immunizations followed by a boost after 16 weeks. The second regimen will follow the same dosing and administering schedule, but without the boost after 16 weeks to study if a boost may be necessary. The third regimen will follow the first regimen with the interval duration to the boost shortened to only 4 weeks. In the fourth and final regimen, the vaccine will be administered two times instead of four followed by a boost in 4 weeks to evaluate if two priming immunizations will be sufficient to confer protection. In summary: ‐ Group 1: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive normal saline (NS) placebo on Days 1, 3, 5, 7, and 113. ‐ Group 2: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive NS on Days 1, 3, 5, and 7. ‐ Group 3: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive NS on Days 1, 3, 5, 7, and 29. ‐ Group 4: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive NS on Days 1 and 8. The safety and tolerability of each regimen will be measured by recording (1) solicited and unsolicited adverse events, (2) immunogenicity by assessing humoral and cellular immune responses pre‐ and post‐vaccination, and (3) vaccine efficacy (VE) by measuring protection against homologous CHMI administered by DVI of PfSPZ Challenge (NF54) at 8 weeks post‐final vaccination.