Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response
Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8+ T cell response
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疟疾 DNA 疫苗 gp96NTD-CSP 引发 CSP 特异性抗体和 CD8 T 细胞反应
DOI：
10.1007/s00436-015-4429-8
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发表时间：
2015
影响因子：
2
通讯作者：
Wenyue Xu
中科院分区：
文献类型：
--
作者：
Zhangping Tan;Tao;Hong Zheng;Yan Ding;Wenyue Xu
红细胞前期亚单位疫苗既能诱导CSP特异性抗体，又能诱导CD 8 + T细胞应答。本研究设计了一种新的疟疾DNA疫苗gp 96 NTD-CSP，并对其免疫保护效果进行了研究。我们发现gp 96 NTD-CSP融合蛋白在转染后主要分布于真核细胞表面，并能被宿主免疫系统感知为“危险信号”。有趣的是，用gp 96 NTD-CSP免疫的小鼠中的肝寄生虫负荷和寄生虫血症均显著低于用gp 96 NTD、CSP或gp 96 NTD-SYVPSAEQI免疫的小鼠中的那些，gp 96 NTD-SYVPSAEQI通过将CSP特异性CD 8 + T细胞表位与用KDEL缺失的gp 96的N-末端结构域融合而构建。结果表明，gp 96 NTD-CSP免疫小鼠的CSP特异性抗体水平和分泌IFN-γ的CSP特异性CD 8 + T细胞频率均显著高于gp 96 NTD、CSP和gp 96 NTD-SYVPSAEQI免疫小鼠。结果表明，gp 96 NTD-CSP DNA疫苗能诱导小鼠产生体液免疫和细胞免疫应答，这与gp 96 NTD和全长CSP的佐剂效应有关。
It is ideal for the pre-erythrocytic stage subunit vaccine to induce both CSP-specific antibody and CD8+ T cell response. Here, we designed a novel malaria DNA vaccine gp96NTD-CSP, which was constructed by fusing the full-length of CSP with the N-terminal domain of gp96 that deleted the endoplasmic reticulum-localized motif KDEL, and investigated its protective efficacy. We found that the fusion protein gp96NTD-CSP was mainly distributed on the surface of eukaryotic cells after transfection and could be sensed as a “danger signal” by the host immune system. Interestingly, both liver parasite burden and parasitemia in mice immunized with gp96NTD-CSP were significantly lower than those in the mice immunized either with gp96NTD, CSP, or gp96NTD-SYVPSAEQI, which was constructed by fusing the CSP-specific CD8+ T cell epitope with the N-terminal domain of gp96 deleted with KDEL. Consistently, both the level of CSP-specific antibody and the frequency of IFN-γ secreted-CSP-specific CD8+ T cells were much higher in mice immunized with gp96NTD-CSP than those in the mice immunized either with gp96NTD, CSP, or gp96NTD-SYVPSAEQI. Our results suggest that the malaria DNA vaccine gp96NTD-CSP could induce both humoral and cellular immune responses, which is attributed to the adjuvant effect of gp96NTD and full-length CSP.
影响因子：
6.4
作者：
Jobe, Ousman;Lumsden, Joanne;Krzych, Urszula
通讯作者：
Krzych, Urszula