Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults.
Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults.
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DOI：
10.4269/ajtmh.20-0435
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Hoffman SL
中科院分区：
文献类型：
--
作者：
Jongo SA;Urbano V;Church LWP;Olotu A;Manock SR;Schindler T;Mtoro A;Kc N;Hamad A;Nyakarungu E;Mpina M;Deal A;Bijeri JR;Ondo Mangue ME;Ntutumu Pasialo BE;Nguema GN;Owono SN;Rivas MR;Chemba M;Kassim KR;James ER;Stabler TC;Abebe Y;Saverino E;Sax J;Hosch S;Tumbo AM;Gondwe L;Segura JL;Falla CC;Phiri WP;Hergott DEB;García GA;Schwabe C;Maas CD;Murshedkar T;Billingsley PF;Tanner M;Ayekaba MO;Sim BKL;Daubenberger C;Richie TL;Abdulla S;Hoffman SL
恶性疟原虫子孢子(PfSPZ)疫苗(辐射减毒、无菌、纯化、冷冻保存的PfSPZ)和PfSPZ-CVac(每周接受氯喹化学预防的受试者接种感染、无菌、纯化、冷冻保存的PfSPZ)对非免疫成人的同源控制性人类疟疾感染(CHMI)显示出100%的疫苗效果(VES)。恶性疟原虫子孢子-CVac从未在非洲接种疫苗的人中被评估为CHMI。我们采用随机、双盲、安慰剂对照和平行试验的方法，评价了3剂2.7×106PfSPZ疫苗和3剂1.0×105PfSPZ-CVAc疫苗的安全性、免疫原性和抗同源CHMI的VE。接种者与生理盐水对照组、PfSPZ疫苗与PfSPZ-CVac接受者在接种研究产品后6天内的不良事件发生率均无差异。然而，从第7天到第13天，接受PfSPZ-CVAC的患者有明显更多的AEs，可能是由于PF寄生虫血症。在CHMI时，PfSPZ疫苗接受者的抗体应答是PfSPZ-CVac接受者的2.9倍。末次接种后14周的中位有效率为55%(8/13，P=0.051)，15周的中位有效率为27%(5/15，P=0.32)。在PfSPZ-CVac接受者中，55%的VE较高，而剂量低27倍，这可能是由于寄生虫在肝脏中后期成熟的结果，导致对更多数量和更广泛的抗原的细胞免疫诱导。
Plasmodium falciparum 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. Plasmodium falciparum 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 × 106 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 105 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, P = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, P = 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.
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影响因子：
3.3
作者：
Jongo, Said A.;Shekalaghe, Seif A.;Hoffman, Stephen L.
通讯作者：
Hoffman, Stephen L.
影响因子：
3
作者：
Cook J;Hergott D;Phiri W;Rivas MR;Bradley J;Segura L;Garcia G;Schwabe C;Kleinschmidt I
通讯作者：
Kleinschmidt I
影响因子：
5.2
作者：
Hodgson, Susanne H.;Juma, Elizabeth;Marsh, Kevin
通讯作者：
Marsh, Kevin
影响因子：
3
作者：
Mordmueller, Benjamin;Supan, Christian;Kremsner, Peter G.
通讯作者：
Kremsner, Peter G.
影响因子：
82.9
作者：
Ishizuka, Andrew S.;Lyke, Kirsten E.;Seder, Robert A.
通讯作者：
Seder, Robert A.