小柯机器人

美国哈佛医学院Ivan Zanoni研究小组的最新研究表明通过调节微生物配体的物理性质可扩展抗原的免疫原性。2022年2月10日出版的《细胞》杂志发表了这项成果。

通过对真菌甘露聚糖的研究，研究人员发现模式识别受体(PRR)配体的物理形式决定了免疫反应。可溶性甘露聚糖在外周系统是免疫沉默的，但会在引流淋巴结(dLN)中引发有效的促炎反应。通过调节甘露聚糖的物理性质，研究人员研发了一种针对外围和dLN的小分子。当与病毒糖蛋白抗原结合时，这种甘露聚糖制剂拓宽了表位识别，引发有效的抗原特异性中和抗体，并提供对肺部病毒感染的保护。因此，微生物配体的物理特性决定了免疫反应的结果，这可用于疫苗研发。

据了解，通过PRR激活先天免疫系统是产生持久适应性免疫的关键。PRR识别与入侵微生物相关的独特化学模式，但关于PRR配体的物理特性是否以及如何影响免疫反应进程仍然未知。

附：英文原文

Title: An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity

Author: Francesco Borriello, Valentina Poli, Ellen Shrock, Roberto Spreafico, Xin Liu, Novalia Pishesha, Claire Carpenet, Janet Chou, Marco Di Gioia, Marisa E. McGrath, Carly A. Dillen, Nora A. Barrett, Lucrezia Lacanfora, Marcella E. Franco, Laura Marongiu, Yoichiro Iwakura, Ferdinando Pucci, Michael D. Kruppa, Zuchao Ma, Douglas W. Lowman, Harry E. Ensley, Etsuro Nanishi, Yoshine Saito, Timothy R. O’Meara, Hyuk-Soo Seo, Sirano Dhe-Paganon, David J. Dowling, Matthew Frieman, Stephen J. Elledge, Ofer Levy, Darrell J. Irvine, Hidde L. Ploegh, David L. Williams, Ivan Zanoni

Issue&Volume: 2022-02-10

Abstract: Activation of the innate immune system via pattern recognition receptors (PRRs) iskey to generate lasting adaptive immunity. PRRs detect unique chemical patterns associatedwith invading microorganisms, but whether and how the physical properties of PRR ligandsinfluence the development of the immune response remains unknown. Through the studyof fungal mannans, we show that the physical form of PRR ligands dictates the immuneresponse. Soluble mannans are immunosilent in the periphery but elicit a potent pro-inflammatoryresponse in the draining lymph node (dLN). By modulating the physical form of mannans,we developed a formulation that targets both the periphery and the dLN. When combinedwith viral glycoprotein antigens, this mannan formulation broadens epitope recognition,elicits potent antigen-specific neutralizing antibodies, and confers protection againstviral infections of the lung. Thus, the physical properties of microbial ligands determinethe outcome of the immune response and can be harnessed for vaccine development.

DOI: 10.1016/j.cell.2022.01.009

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00067-8