A potent malaria vaccine based on adenovirus with dual modifications at Hexon and pVII.
A potent malaria vaccine based on adenovirus with dual modifications at Hexon and pVII.
复制标题
DOI：
10.1016/j.vaccine.2017.10.066
复制
发表时间：
2017-12-15
期刊：
影响因子：
5.5
通讯作者：
Tsuji M
中科院分区：
文献类型：
--
作者：
Shiratsuchi T;Rai U;Kaneko I;Zhang M;Iwanaga S;Yuda M;Tsuji M
腺病毒(Ad)被认为是针对其肝脏阶段的疟疾疫苗最有前途的平台之一，因为它能够诱导针对转基因的强大T细胞反应。然而，这一平台还需要进一步改进，以激发对抗疟疾的另一种免疫力，即体液反应。为了提高恶性疟原虫环子孢子蛋白(PfCSP)基因疫苗的免疫原性和保护性，我们在PfCSP基因的基础上，将恶性疟原虫环子孢子蛋白(PfCSP)的B细胞和CD4+T细胞表位分别插入到Ad的衣壳蛋白Hexon和核心蛋白VII(PVII)中。与只表达PfCSP转基因的Ad疫苗AdPfCSP相比，将PfCSP衍生的B细胞表位插入Hexon显著增强了表位特异性抗体应答。PfCSP衍生的CD4+T细胞表位插入pVII不仅增强了PfCSP特异性的CD4+T细胞应答，而且增强了抗PfCSP抗体应答。最后，同时具有六邻体和pVII基因修饰的AdPfCSP免疫的小鼠比AdPfCSP或六邻体修饰的AdPfCSP免疫的小鼠更能抵抗表达PfCSP的转基因鼠疟原虫的攻击。总体而言，这项研究表明，六邻体和pVII修饰的AdPfCSP疫苗是一种很有前途的疟疾疫苗，它能诱导强烈的PfCSP特异性体液、CD4+T细胞和CD8+T细胞反应，并预防表达PfCSP的转基因疟疾寄生虫的感染。
Adenovirus (Ad) is thought to be one of the most promising platforms for a malaria vaccine targeted against its liver stages, because of its ability to induce a strong T-cell response against a transgene. However, a further improvement of this platform is needed in order to elicit another arm of the immunity, i.e. humoral response, against malaria. In order to augment immunogenicity and protective efficacy of Ad-based malaria vaccine, we inserted B cell, as well as CD4+ T cell, epitopes of Plasmodium falciparum circumsporozoite protein (PfCSP) into the capsid protein, Hexon, and the core protein, VII (pVII), of Ad, respectively, in addition to the PfCSP transgene. Insertion of PfCSP-derived B cell epitope to Hexon significantly enhanced the epitope-specific antibody response compared to AdPfCSP, an Ad vaccine expressing only PfCSP transgene. PfCSP-derived CD4+ T cell epitope insertion into pVII augmented not only PfCSP-specific CD4+ T cell response but also anti-PfCSP antibody response. Finally, mice immunized with AdPfCSP having both Hexon and pVII modifications were more protected than AdPfCSP or Hexon-modified AdPfCSP against challenge with transgenic rodent malaria parasites expressing the PfCSP. Overall, this study has demonstrated that Hexon and pVII-modified AdPfCSP vaccine is a promising malaria vaccine which induces strong PfCSP-specific humoral, CD4+ T cell, and CD8+ T cell responses and protects against infection with transgenic malaria parasites expressing the PfCSP.
登录
查看更多内容
影响因子：
3.1
作者：
Karen, Kasey A.;Deal, Cailin;Ketner, Gary
通讯作者：
Ketner, Gary
影响因子：
4.4
作者：
Persson, C;Oliveira, GA;Nardin, E
通讯作者：
Nardin, E
影响因子：
15.9
作者：
Shiratsuchi, Takayuki;Rai, Urvashi;Tsuji, Moriya
通讯作者：
Tsuji, Moriya
影响因子：
158.5
作者：
Mian-McCarthy, Sara;Agnandji, Selidji Todagbe;Vansadia, Preeti
通讯作者：
Vansadia, Preeti
影响因子：
4.4
作者：
Doolan, DL;Hoffman, SL
通讯作者：
Hoffman, SL