1Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, Tanzania.
2Ministry of Health and Social Welfare, Government of Equatorial Guinea, Bioko Norte, Equatorial Guinea.
Am J Trop Med Hyg. 2021 Jan;104(1):283-293. doi: 10.4269/ajtmh.20-0435.
sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.7 × 10 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 10 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm randomized, double-blind, placebo-controlled, and conducted in parallel. There were no differences in solicited adverse events between vaccinees and normal saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 days after administration of investigational product. However, from days 7-13, PfSPZ-CVac recipients had significantly more AEs, probably because of Pf parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, = 0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose was likely a result of later stage parasite maturation in the liver, leading to induction of cellular immunity against a greater quantity and broader array of antigens.
疟原虫孢子（PfSPZ）疫苗（经辐射减毒、无菌、纯化、冷冻保存的 PfSPZ）和 PfSPZ-CVac（接种每周氯喹化学预防的受种者的感染性、无菌、纯化、冷冻保存的 PfSPZ）在非免疫成人中针对同源对照性人类疟疾感染（CHMI）的疫苗效力（VE）均为 100%。疟原虫孢子-CVac 从未在非洲疫苗接种者中针对 CHMI 进行过评估。我们评估了三剂 2.7×10 PfSPZ 的 PfSPZ 疫苗（间隔 8 周）和三剂 1.0×10 PfSPZ 的 PfSPZ-CVac（间隔 4 周）的安全性、免疫原性和针对同源 CHMI 的 VE，每个臂均采用随机、双盲、安慰剂对照设计，并平行进行。在研究产品给药后 6 天内，疫苗接种者与生理盐水对照组之间或 PfSPZ 疫苗与 PfSPZ-CVac 受种者之间，在募集的不良事件方面没有差异。然而，从第 7 天到第 13 天，PfSPZ-CVac 受种者的 AE 明显更多，可能是由于 Pf 寄生虫血症所致。在 CHMI 时，PfSPZ 疫苗受种者的抗体反应比 PfSPZ-CVac 受种者高 2.9 倍。在最后一剂 PfSPZ-CVac 后中位数为 14 周时，疫苗效力为 55%（13 例中的 8 例，=0.051），在最后一剂 PfSPZ 疫苗后中位数为 15 周时，疫苗效力为 27%（15 例中的 5 例，=0.32）。PfSPZ-CVac 受种者的 VE 为 55%，剂量低 27 倍，这可能是由于肝脏中寄生虫成熟的后期阶段，导致针对更多数量和更广泛抗原的细胞免疫诱导。
