Protection against Plasmodium falciparum malaria by PfSPZ Vaccine
Protection against Plasmodium falciparum malaria by PfSPZ Vaccine
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DOI：
10.1172/jci.insight.89154
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发表时间：
2017-01-12
期刊：
影响因子：
8
通讯作者：
Hoffman, Stephen L.
中科院分区：
文献类型：
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作者：
Epstein, Judith E.;Paolino, Kristopher M.;Hoffman, Stephen L.
背景：一种放射性减毒恶性疟原虫（Pf）孢子虫（SPZ）疟疾疫苗，PfSPZ疫苗，在5次静脉注射后3周，使6名受试者中的6人（100%）免受同源Pf（与疫苗中的菌株相同）控制的人疟疾感染（CHMI）。下一步是在较少剂量和24周后评估对异源Pf（不同于疫苗中的Pf）的保护功效。方法：该试验评估了3剂或5剂PfSPZ疫苗在无免疫受试者中直接静脉接种（DVI）的耐受性、安全性、免疫原性和保护效果。结果：末次免疫后3周，5剂2.7 × 10(5) PfSPZ对13名受者中的12人（92.3% [95% CI: 48.0, 99.8]）和5名受者中的4人（80.0%[10.4,99.5]）具有抗同源CHMI的保护作用；3剂4.5 × 10(5) PfSPZ可保护15人中的13人（86.7%[35.9,98.3]）免受同源CHMI的侵害。在最后一次免疫24周后，5剂方案保护7 / 10（70.0%[17.3,93.3]）和1 / 10（10.0%[-35.8,45.6]）免受同源CHMI的侵害；3次给药方案保护了14人中8人（57.1%[21.5,76.6]）免受同源CHMI的侵害。所有22例对照均发生Pf寄生虫病。PfSPZ疫苗耐受性好，安全，易于使用。没有抗体或T细胞反应与保护相关。结论：据我们所知，我们首次证明了PfSPZ疫苗可以在有限的疟疾初发成人受试者中预防3周异源CHMI。在该人群中，3剂量方案可预防3周和24周的同源CHMI（分别为87%和57%）。这些结果为制定预防疟疾的最佳免疫方案提供了基础。
BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks.METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects.RESULTS: Three weeks after final immunization, 5 doses of 2.7 x 10(5) PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 x 10(5) PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [-35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection.CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria.