Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope.
Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope.
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自组装的肽纳米纤维可提高针对疟疾表位的耐用抗体反应。
DOI：
10.1016/j.biomaterials.2012.05.041
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发表时间：
2012-09
期刊：
影响因子：
14
通讯作者：
Collier, Joel H.
中科院分区：
文献类型：
--
作者：
Rudra, Jai S.;Mishra, Satish;Chong, Anita S.;Mitchell, Robert A.;Nardin, Elizabeth H.;Nussenzweig, Victor;Collier, Joel H.
调节先天和获得性免疫反应的生物材料正受到越来越多的关注，作为针对各种疾病的保护性免疫的佐剂。以前的研究结果表明，自组装的β-Sheet多肽与短肽表位融合后，可以作为有效的佐剂，诱导强大而持久的抗体反应。在这里，我们研究了恶性疟原虫环子孢子蛋白(CS)蛋白的多肽表位(NANP)3与自组装多肽结构域Q11结合的免疫原性和抗体应答的质量。在MyD88、NALP3、TLR-2或TLR-5功能受损的基因敲除小鼠中研究了佐剂作用的机制，并用疟疾感染的转基因子孢子中和试验(TSN)评估了抗(NANP)3-Q11抗体的质量。(NANP)3-Q11自组装成纳米纤维，并在C57BL/6小鼠体内持续抗体反应长达40周。抗体反应依赖于T细胞和MyD88。用辐照的子孢子或合成的多肽(T1BT*)4-P3C免疫，并用(NANP)3-Q11增强免疫的小鼠血清，在TSN检测中，抗体滴度显著升高，子孢子感染显著抑制。此外，两个不同的表位可以在不影响针对其中任何一个的抗体反应的强度或持续时间的情况下自组装在一起，使这些材料成为自我调节多抗原免疫治疗的良好平台。
Biomaterials that modulate innate and adaptive immune responses are receiving increasing interest as adjuvants for eliciting protective immunity against a variety of diseases. Previous results have indicated that self-assembling β-sheet peptides, when fused with short peptide epitopes, can act as effective adjuvants and elicit robust and long-lived antibody responses. Here we investigated the mechanism of immunogenicity and the quality of antibody responses raised by a peptide epitope from P. falciparum circumsporozoite (CS) protein, (NANP)3,conjugated to the self-assembling peptide domain Q11. The mechanism of adjuvant action was investigated in knockout mice with impaired MyD88, NALP3, TLR-2, or TLR-5 function, and the quality of antibodies raised against (NANP)3-Q11 was assessed using a transgenic sporozoite neutralizing (TSN) assay for malaria infection. (NANP)3-Q11 self-assembled into nanofibers, and antibody responses lasted up to 40 weeks in C57BL/6 mice. The antibody responses were T cell- and MyD88-dependent. Sera from mice primed with either irradiated sporozoites or a synthetic peptide, (T1BT*)4-P3C, and boosted with (NANP)3-Q11 showed significant increases in antibody titers and significant inhibition of sporozoite infection in TSN assays. In addition, two different epitopes could be self-assembled together without compromising the strength or duration of the antibody responses raised against either of them, making these materials promising platforms for self-adjuvanting multi-antigenic immunotherapies.
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影响因子：
2.9
作者：
Jones, Kim S.
通讯作者：
Jones, Kim S.
影响因子：
5.4
作者：
Braun, Marion;Jandus, Camilla;Romero, Pedro
通讯作者：
Romero, Pedro
影响因子：
16.6
作者：
Boato, Francesca;Thomas, Richard M.;Robinson, John A.
通讯作者：
Robinson, John A.
影响因子：
3.7
作者：
Carcaboso, AM;Hernández, RM;Pedraz, JL
通讯作者：
Pedraz, JL
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