Galassie Allison C, Goll Johannes B, Samir Parimal, Jensen Travis L, Hoek Kristen L, Howard Leigh M, Allos Tara M, Niu Xinnan, Gordy Laura E, Creech C Buddy, Hill Heather, Joyce Sebastian, Edwards Kathryn M, Link Andrew J
Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
The Emmes Corporation, Rockville, MD, USA.
Proteomics. 2017 Jun;17(12). doi: 10.1002/pmic.201600453.
Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer cells, T cells, and B cells after administration of either an Adjuvant System 03 adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA class I proteins was increased in the Adjuvant System 03 group. We identified several protein families whose proteomic responses predicted seroprotective antibody responses (>1:40 hemagglutination inhibition titer), including inflammation and oxidative stress proteins at day 1 as well as immunoproteasome subunit (PSME1 and PSME2) and HLA class I proteins at day 3 in monocytes. While comparison between temporal proteomic and transcriptomic results showed little overlap overall, enrichment of the MHC class I antigen processing and presentation pathway in monocytes and neutrophils was confirmed by both approaches.
佐剂通过人们知之甚少的机制增强疫苗引发的免疫反应。我们采用系统生物学方法，研究了接种含佐剂系统03的佐剂或不含佐剂的裂解病毒H5N1流感疫苗后，五种主要人类免疫细胞群体（中性粒细胞、单核细胞、自然杀伤细胞、T细胞和B细胞）中蛋白质表达随时间的变化。单核细胞在疫苗组之间表现出最强的差异信号。接种疫苗后第3天，包括MHC I类介导的抗原加工和呈递在内的几种抗原呈递相关途径在单核细胞和中性粒细胞中富集，且佐剂系统03组中HLA I类蛋白的表达增加。我们鉴定了几个蛋白质家族，其蛋白质组学反应可预测血清保护性抗体反应（血凝抑制效价>1:40），包括第1天的炎症和氧化应激蛋白，以及第3天单核细胞中的免疫蛋白酶体亚基（PSME1和PSME2）和HLA I类蛋白。虽然蛋白质组学和转录组学结果的时间比较总体上显示重叠很少，但两种方法均证实了单核细胞和中性粒细胞中MHC I类抗原加工和呈递途径的富集。
