Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection
Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection
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DOI：
10.1073/pnas.1615324114
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发表时间：
2017-03-07
影响因子：
11.1
通讯作者：
Seder, Robert A.
中科院分区：
文献类型：
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作者：
Lyke, Kirsten E.;Ishizuka, Andrew S.;Seder, Robert A.
一种减毒疟疾活疫苗，即恶性疟原虫孢子子疫苗（PfSPZ疫苗），在最终接种疫苗后14个月内，可提供无菌保护，防止与疫苗菌株同源的恶性疟原虫（Pf）寄生虫感染受控制的人疟疾。没有一种注射疟疾疫苗显示使用与疫苗株异源的Pf寄生虫对CHMI具有长期保护作用。在这里，我们对15名未患疟疾的成年人进行了一项开放标签试验，接种剂量为9.0 x 10(5) PfSPZ的PfSPZ疫苗，每隔8周静脉注射3次。在最终免疫19周后，14名（95% CI, 35-87%）接种疫苗的志愿者中有9名（64%）没有寄生虫病，而6名未接种疫苗的对照组中没有寄生虫病（P = 0.012）。在9名非寄生虫患者中，6名在最终免疫后33周用异源Pf7G8寄生虫重复CHMI。6人中有5人（83%）（95% CI, 36-99%）没有寄生虫病，而6名未接种疫苗的对照组中没有寄生虫病。在所有疫苗接种者中检测到PfSPZ特异性t细胞和抗体反应。同种（NF54）或异种（7G8） PfSPZ体外刺激接种者T细胞产生的细胞因子高度相关。有趣的是，血液中pfspz特异性t细胞反应在第一次免疫后达到峰值，并且在随后的免疫中没有增强。总的来说，这些数据表明，PfSPZ疫苗可以实现对同源和异源Pf寄生虫的持久保护。正在进行的研究将确定是否可以通过进一步改变疫苗剂量和免疫接种次数来增强保护效果。
A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 x 10(5) PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ- specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.