Protection against malaria at 1 year and immune correlates following PfSPZ vaccination
Protection against malaria at 1 year and immune correlates following PfSPZ vaccination
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DOI：
10.1038/nm.4110
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发表时间：
2016-06-01
期刊：
影响因子：
82.9
通讯作者：
Seder, Robert A.
中科院分区：
文献类型：
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作者：
Ishizuka, Andrew S.;Lyke, Kirsten E.;Seder, Robert A.
减毒恶性疟原虫（Pf）子孢子（SPZ）疫苗PfSPZ疫苗在免疫后3周对受控人类疟疾感染（CHMI）具有高度保护性，但保护的持久性尚不清楚。我们评估了疫苗剂量、方案和给药途径如何影响疟疾初治成人的持久保护。在用2.7 × 10（5）PfSPZ进行4次静脉免疫后，6/11（55%）接种受试者在CHMI后21周保持无寄生虫血症。来自该剂量组的5名非寄生虫血症受试者在第59周时接受了重复CHMI，没有人出现寄生虫血症。虽然PF特异性血清抗体水平与免疫后21-25周的保护相关，但抗体水平在59周时大幅下降。到第59周，血液中的PF特异性T细胞反应也下降。为了确定血液中的T细胞应答是否反映肝脏中的应答，我们用PfSPZ疫苗接种非人灵长类动物。Pf-specific干扰素-g-生产CD 8 T细胞在肝脏中的频率比血液中高出100倍。我们的研究结果表明，PfSPZ疫苗通过长寿命的组织驻留T细胞对疟疾提供持久的保护，并且给予更高剂量可能会进一步增强保护。
An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.7 x 10(5) PfSPZ, 6/11 (55%) vaccinated subjects remained without parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic subjects from this dosage group underwent repeat CHMI at 59 weeks, and none developed parasitemia. Although Pf-specific serum antibody levels correlated with protection up to 21-25 weeks after immunization, antibody levels waned substantially by 59 weeks. Pf-specific T cell responses also declined in blood by 59 weeks. To determine whether T cell responses in blood reflected responses in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific interferon-g-producing CD8 T cells were present at similar to 100-fold higher frequencies in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection.