Protective antibody and CD8+ T-cell responses to the Plasmodium falciparum circumsporozoite protein induced by a nanoparticle vaccine.
Protective antibody and CD8+ T-cell responses to the Plasmodium falciparum circumsporozoite protein induced by a nanoparticle vaccine.
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DOI：
10.1371/journal.pone.0048304
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lanar DE
中科院分区：
文献类型：
--
作者：
Kaba SA;McCoy ME;Doll TA;Brando C;Guo Q;Dasgupta D;Yang Y;Mittelholzer C;Spaccapelo R;Crisanti A;Burkhard P;Lanar DE
全世界的疟疾负担仍然是一个主要的公共卫生问题，部分原因是缺乏针对恶性疟原虫寄生虫的有效疫苗。有效的疫苗很可能需要诱导抗原特异性CD 8+和CD 4 + T细胞以及持久的抗体应答，所有这些都协同工作以消除感染。我们在此报告了对自组装蛋白纳米颗粒（SAPN）疫苗的有效修饰，所述自组装蛋白纳米颗粒（SAPN）疫苗先前在啮齿动物模型中被证明有效控制伯氏疟原虫感染，现在在能够用于人类受试者的平台中呈现人类恶性疟原虫的B-和T-细胞表位。为了建立基于SAP N的疫苗的基础，将来自恶性疟原虫环子孢子蛋白（PfCSP）的B-和CD 8 + T细胞表位和通用CD 4 T辅助表位PADRE工程化为通用小蛋白（约125个氨基酸），其自组装成重复展示所选表位的球形纳米颗粒。使用表达人疟疾全长恶性疟原虫环子孢子蛋白（Tg-Pb/PfCSP）的小鼠的转基因伯氏疟原虫疟疾寄生虫，在小鼠中评价恶性疟原虫表位特异性免疫应答。我们表明，在盐水中递送的SAPN构建体可以诱导高滴度、持久（1年）的保护性抗体和多功能（IFNγ+、IL-2+）长寿的中枢记忆CD 8 + T细胞。此外，我们证明了这些Ab或CD 8 + T细胞可以独立地提供无菌保护，以对抗转基因寄生虫的致命攻击。SAPN构建体诱导针对恶性疟原虫环子孢子蛋白（PfCSP）的表位特异性序列的持久抗体和细胞免疫应答，并防止小鼠中显示全长PfCSP的转基因伯氏疟原虫感染。
The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8+ and CD4+ T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects. To establish the basis for a SAPN-based vaccine, B- and CD8+ T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year) protective antibody and poly-functional (IFNγ+, IL-2+) long-lived central memory CD8+ T-cells. Furthermore, we demonstrated that these Ab or CD8+ T–cells can independently provide sterile protection against a lethal challenge of the transgenic parasites. The SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP.
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DOI：
10.4049/jimmunol.0901957
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaba SA;Brando C;Guo Q;Mittelholzer C;Raman S;Tropel D;Aebi U;Burkhard P;Lanar DE
通讯作者：
Lanar DE
影响因子：
14.9
作者：
Gonzalez-Galarza FF;Christmas S;Middleton D;Jones AR
通讯作者：
Jones AR
影响因子：
5.5
作者：
Minigo, Gabriela;Scholzen, Anja;Plebanski, Magdalena
通讯作者：
Plebanski, Magdalena
影响因子：
4.4
作者：
Alexander, J;Oseroff, C;Sette, A
通讯作者：
Sette, A
影响因子：
6.7
作者：
Cockburn IA;Tse SW;Radtke AJ;Srinivasan P;Chen YC;Sinnis P;Zavala F
通讯作者：
Zavala F