A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates
A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates
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DOI：
10.1126/scitranslmed.aaa3043
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发表时间：
2015-06-03
影响因子：
17.1
通讯作者：
Valenzuela, Jesus G.
中科院分区：
文献类型：
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作者：
Oliveira, Fabiano;Rowton, Edgar;Valenzuela, Jesus G.
目前，还没有商业上可用的针对利什曼病的人类疫苗。在啮齿动物中，对沙蝇载体唾液蛋白的细胞免疫与预防利什曼病有关，使它们成为值得进一步探索的疫苗目标。我们证明，暴露于未感染沙蝇叮咬或唾液蛋白PdSP15免疫的非人类灵长类动物(NHP)对感染叮咬引发的皮肤利什曼病具有保护作用。与对照组相比，暴露于未感染沙蝇和10只PdSP15免疫猕猴中的7只猕猴的疾病和寄生虫负担显著降低。保护与利什曼原虫特异性CD4(+)干扰素-伽马(+)淋巴细胞的早期出现有关，这表明对唾液或PdSP15的免疫增强了宿主对寄生虫的免疫反应，同时保持了最低限度的病理。值得注意的是，30%无保护的PdSP15免疫的NHP既没有对PdSP15的免疫力，也没有加速的利什曼原虫特异性免疫。自然暴露于杜氏疟原虫叮咬的个体的血清和外周血单核细胞识别PdSP15，证明了其在人类中的免疫原性。PdSP15的序列和结构与哺乳动物的蛋白质没有同源性，进一步表明它有可能成为人类利什曼病疫苗的组成部分。
Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly-exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4(+)IFN-gamma(+) lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.