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Amino acid starvation enhances vaccine efficacy by augmenting neutralizing antibody production.
Science Signaling ( IF 7.3 ) Pub Date : 2019-11-12 , DOI: 10.1126/scisignal.aav4717
Sumbul Afroz 1 , Shama 1 , Srikanth Battu 1 , Shaikh Matin 1 , Sabrina Solouki 2 , Jessica P Elmore 2 , Gillipsie Minhas 1 , Weishan Huang 2, 3 , Avery August 2 , Nooruddin Khan 1
Affiliation  

Specific reduction in the intake of proteins or amino acids (AAs) offers enormous health benefits, including increased life span, protection against age-associated disorders, and improved metabolic fitness and immunity. Cells respond to conditions of AA starvation by activating the amino acid starvation response (AAR). Here, we showed that mimicking AAR with halofuginone (HF) enhanced the magnitude and affinity of neutralizing, antigen-specific antibody responses in mice immunized with dengue virus envelope domain III protein (DENVrEDIII), a potent vaccine candidate against DENV. HF enhanced the formation of germinal centers (GCs) and increased the production of the cytokine IL-10 in the secondary lymphoid organs of vaccinated mice. Furthermore, HF promoted the transcription of genes associated with memory B cell formation and maintenance and maturation of GCs in the draining lymph nodes of vaccinated mice. The increased abundance of IL-10 in HF-preconditioned mice correlated with enhanced GC responses and may promote the establishment of long-lived plasma cells that secrete antigen-specific, high-affinity antibodies. Thus, these data suggest that mimetics of AA starvation could provide an alternative strategy to augment the efficacy of vaccines against dengue and other infectious diseases.

中文翻译:

氨基酸饥饿会通过增加中和抗体的产生来增强疫苗效力。

蛋白质或氨基酸(AAs)摄入量的特定减少可带来巨大的健康益处,包括延长寿命,防止与年龄相关的疾病以及改善代谢适应性和免疫力。细胞通过激活氨基酸饥饿反应(AAR)对AA饥饿条件作出反应。在这里,我们显示了用氟氟龙酮(HF)模仿AAR增强了用登革病毒包膜域III蛋白(DENVrEDIII)(一种针对DENV的强效候选疫苗)免疫的小鼠的中和抗原特异性抗体反应的强度和亲和力。HF增强了接种小鼠次生淋巴器官中生发中心(GCs)的形成并增加了细胞因子IL-10的产生。此外,HF促进了与记忆B细胞形成相关的基因的转录,以及在免疫小鼠的引流淋巴结中GC的维持和成熟。HF预处理小鼠中IL-10丰度的增加与GC反应增强相关,并可能促进分泌抗原特异性,高亲和力抗体的长寿浆细胞的建立。因此,这些数据表明,AA饥饿的模拟物可以提供替代策略,以增强疫苗抵抗登革热和其他传染性疾病的功效。
更新日期:2019-11-13
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