A nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria.
A nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria.
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DOI：
10.4049/jimmunol.0901957
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发表时间：
2009-12-01
期刊：
影响因子：
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通讯作者：
Lanar DE
中科院分区：
文献类型：
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作者：
Kaba SA;Brando C;Guo Q;Mittelholzer C;Raman S;Tropel D;Aebi U;Burkhard P;Lanar DE
我们设计并生产了一种基于高度通用的自组装多肽纳米颗粒（SAPN）平台的原型疟疾疫苗，该平台可以重复显示抗原表位。我们利用这个平台展示了疟原虫伯氏疟原虫环孢子子蛋白（CSP） B细胞免疫优势重复表位（DPPPPNPN）2D的串联重复序列。在生理盐水中施用，不需要异种佐剂，SAPN构建体P4c-Mal对具有广泛遗传不同免疫背景的小鼠（包括H-2b， H-2d和H-2k等位基因）具有长期的保护性免疫反应。免疫小鼠对B细胞表位产生CD4+ T细胞依赖性、高滴度、持久、高亲和力的抗体反应。在最后一次免疫后6个月给予小鼠对寄生虫的初始攻击，或在成功清除寄生虫的初始攻击后给予长达15个月的第二次攻击。此外，我们证明SAPN平台不仅可以传递有序的B细胞肽表位序列，还可以作为典型的免疫载体，为P4c-Mal特异性B细胞提供同源帮助。
We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)2D of the malaria parasite Plasmodium berghei circumsporozoite protein (CSP). Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long lived protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2b, H-2d and H-2k alleles. Immunized mice produced a CD4+ T cell dependent, high titer, long lasting, high avidity antibody response against the B cell epitope. Mice were protected against an initial challenge of parasites given up to 6 months after the last immunization or for up to 15 months against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal specific B cells.