Sterile protection against human malaria by chemoattenuated PfSPZ vaccine
Sterile protection against human malaria by chemoattenuated PfSPZ vaccine
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DOI：
10.1038/nature21060
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发表时间：
2017-02-23
期刊：
影响因子：
64.8
通讯作者：
Kremsner, Peter G.
中科院分区：
文献类型：
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作者：
Mordmueller, Benjamin;Surat, Guezin;Kremsner, Peter G.
高度保护性的疟疾疫苗将极大地促进疟疾的预防和消除以及抗药性寄生虫的遏制（1）。高水平以前仅通过用经蚊子接种的放射减毒的恶性疟原虫（Pf）子孢子（PfSPZ）进行免疫接种（2-4）;通过静脉注射无菌的、纯化的、放射减毒的、冷冻保存的PfSPZ，（“PfSPZ疫苗”）（5，6）;或通过蚊子接种给服用氯喹（7-10）或甲氟喹（11）的志愿者的传染性PfSPZ（用子孢子进行化学预防）。我们通过直接静脉接种无菌、纯化、冷冻保存、未辐照的PfSPZ（“PfSPZ挑战”（12，13））来评估免疫接种，这些志愿者服用氯喹进行抗疟疾化学预防（疫苗方法表示为PfSPZ-CVac）（14）。间隔28天的三剂5.12 × 10（4）PfSPZ的PfSPZ攻击（12，13）耐受性良好且安全，并且在最后一剂（组III）后10周进行受控人疟疾感染的9名志愿者中的9名（100%）中预防了感染。保护效果依赖于剂量和方案。用3.2 × 10（3）（组I）或1.28 × 10（4）（组II）PfSPZ免疫分别保护了9名志愿者中的3名（33%）或9名志愿者中的6名（67%）。5天间隔3次5.12 × 10（4）PfSPZ给药保护了8名志愿者中的5名（63%）。PF特异性多功能CD 4记忆T细胞的频率与保护相关。在7，455肽Pf蛋白质组阵列上，来自9个III组疫苗接种者中的至少5个的免疫血清识别22种蛋白质中的每一种。PfSPZ-CVac是一种非常有效的候选疫苗;当我们能够优化免疫方案（剂量、剂量间隔和药物伴侣）时，这种疫苗可用于联合大规模药物给药和大规模疫苗接种计划方法，以消除地理上确定的地区的疟疾。
A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites(1). A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes(2-4); by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine')(5,6); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine(7-10) or mefloquine(11) (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge'(12,13)) to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac)(14). Three doses of 5.12 x 10(4) PfSPZ of PfSPZ Challenge(12,13) at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 x 10(3) (group I) or 1.28 x 10(4) (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 x 10(4) PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.