HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.

HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.
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肽纳米纤维上的HIV包膜抗原价调节抗体大小和结合宽度。

DOI:
10.1038/s41598-021-93702-x
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发表时间:
2021-07-14
期刊:
影响因子:
4.6
通讯作者:
Collier JH
Collier JH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fries CN;Chen JL;Dennis ML;Votaw NL;Eudailey J;Watts BE;Hainline KM;Cain DW;Barfield R;Chan C;Moody MA;Haynes BF;Saunders KO;Permar SR;Fouda GG;Collier JH

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开发有效的HIV-1疫苗的一个主要挑战是其病毒包膜的遗传多样性。由于HIV-1病毒株具有广泛的序列,保护性抗体必须能够结合并中和广泛突变的病毒包膜蛋白。目前还没有设计出能在人体内诱导广泛中和或保护性免疫反应的疫苗。基于纳米材料的疫苗已经显示出产生增加的广度和中和效力的抗体和细胞免疫应答的能力。因此,我们已经开发了基于超分子纳米纤维的免疫原,其具有HIV gp 120包膜糖蛋白。这些免疫原产生的抗体应答与可溶性gp 120相比具有增加的幅度和结合宽度。通过改变纳米纤维上的gp 120密度,我们确定增加的抗原效价与增加的抗体强度和生发中心反应相关。这项研究提出了一个概念验证的疫苗平台产生广泛的,高结合抗体反应的HIV-1包膜糖蛋白。
A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutated viral envelope protein. No vaccine has yet been designed which induces broadly neutralizing or protective immune responses against HIV in humans. Nanomaterial-based vaccines have shown the ability to generate antibody and cellular immune responses of increased breadth and neutralization potency. Thus, we have developed supramolecular nanofiber-based immunogens bearing the HIV gp120 envelope glycoprotein. These immunogens generated antibody responses that had increased magnitude and binding breadth compared to soluble gp120. By varying gp120 density on nanofibers, we determined that increased antigen valency was associated with increased antibody magnitude and germinal center responses. This study presents a proof-of-concept for a nanofiber vaccine platform generating broad, high binding antibody responses against the HIV-1 envelope glycoprotein.
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