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HIV 包膜抗原价在肽纳米纤维上的改变调节抗体的量和结合广度。

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

机构信息

Department of Biomedical Engineering, Duke University, 101 Science Dr., Campus, Box 90281, Durham, NC, 27708, USA.

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, 27710, USA.

出版信息

Sci Rep. 2021 Jul 14;11(1):14494. doi: 10.1038/s41598-021-93702-x.

Abstract

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.

摘要

开发有效的 HIV-1 疫苗的主要挑战是其病毒包膜的遗传多样性。由于 HIV-1 毒株表现出广泛的序列,保护性抗体必须能够结合和中和广泛突变的病毒包膜蛋白。目前还没有设计出能够在人体中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显示出能够产生增加广度和中和效力的抗体和细胞免疫反应。因此,我们开发了带有 HIV gp120 包膜糖蛋白的超分子纳米纤维免疫原。与可溶性 gp120 相比,这些免疫原产生的抗体反应具有更高的幅度和结合广度。通过改变纳米纤维上 gp120 的密度,我们确定增加抗原价与增加抗体幅度和生发中心反应有关。这项研究为纳米纤维疫苗平台提供了一个概念验证,该平台针对 HIV-1 包膜糖蛋白产生广泛的高结合抗体反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee4c/8280189/8a76a43e7f94/41598_2021_93702_Fig1_HTML.jpg

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