美国麻省理工学院科赫综合癌症研究所Darrell J. Irvine研究组发现，工程化的免疫原结合明矾佐剂可增强体液免疫。这一研究成果于2020年2月17日发表在国际学术期刊《自然-医学》上。

他们证明免疫原的位点特异性修饰与重复磷酸丝氨酸（pSer）残基组成的短肽增强与明矾的结合并延长免疫原的生物利用度。与传统的明矾吸附的免疫原相比，在明矾中形成的经pSer修饰的免疫原引发了明显的生发中心、抗体、中和抗体、记忆力和长寿的浆细胞反应。

从机制上讲，pSer-免疫原-明矾复合物形成纳米颗粒，这些纳米颗粒运输至淋巴结并通过多价和定向抗原展示触发B细胞活化。B细胞直接摄取抗原修饰的明矾颗粒会上调抗原加工和呈递途径，从而进一步促进B细胞活化。这些数据揭示了明矾作用机理，并介绍了一种易于翻译的方法，可使用临床佐剂显著提高对亚单位疫苗的体液免疫力。

据了解，佐剂对于亚单位疫苗的功效至关重要。氢氧化铝（明矾）是最常用的疫苗佐剂，但其佐剂性通常较弱，并且触发抗体反应的机制仍知之甚少。

附：英文原文

Title: Engineered immunogen binding to alum adjuvant enhances humoral immunity

Author: Tyson J. Moyer, Yu Kato, Wuhbet Abraham, Jason Y. H. Chang, Daniel W. Kulp, Nicki Watson, Hannah L. Turner, Sergey Menis, Robert K. Abbott, Jinal N. Bhiman, Mariane B. Melo, Hayley A. Simon, Sara Herrera-De la Mata, Shu Liang, Gregory Seumois, Yash Agarwal, Na Li, Dennis R. Burton, Andrew B. Ward, William R. Schief, Shane Crotty, Darrell J. Irvine

Issue&Volume: 2020-02-17

Abstract: Adjuvants are central to the efficacy of subunit vaccines. Aluminum hydroxide (alum) is the most commonly used vaccine adjuvant, yet its adjuvanticity is often weak and mechanisms of triggering antibody responses remain poorly understood. We demonstrate that site-specific modification of immunogens with short peptides composed of repeating phosphoserine (pSer) residues enhances binding to alum and prolongs immunogen bioavailability. The pSer-modified immunogens formulated in alum elicited greatly increased germinal center, antibody, neutralizing antibody, memory and long-lived plasma cell responses compared to conventional alum-adsorbed immunogens. Mechanistically, pSer-immunogen:alum complexes form nanoparticles that traffic to lymph nodes and trigger B cell activation through multivalent and oriented antigen display. Direct uptake of antigen-decorated alum particles by B cells upregulated antigen processing and presentation pathways, further enhancing B cell activation. These data provide insights into mechanisms of action of alum and introduce a readily translatable approach to significantly improve humoral immunity to subunit vaccines using a clinical adjuvant.

DOI: 10.1038/s41591-020-0753-3

Source: https://www.nature.com/articles/s41591-020-0753-3