Pentamers not found in the universal proteome can enhance antigen specific immune responses and adjuvant vaccines.
Pentamers not found in the universal proteome can enhance antigen specific immune responses and adjuvant vaccines.
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DOI：
10.1371/journal.pone.0043802
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kobinger GP
中科院分区：
文献类型：
--
作者：
Patel A;Dong JC;Trost B;Richardson JS;Tohme S;Babiuk S;Kusalik A;Kung SK;Kobinger GP
某些短肽在人类中不存在，在通用蛋白质组中很少见或根本不存在。含有稀有氨基酸序列的抗原通常具有很高的免疫原性，并可能激活免疫系统的不同手臂。我们首先使用生物信息学工具分析UniProtKB数据库，生成了一系列罕见的、半常见的和常见的5-聚肽。实验观察表明，与常见序列相比，罕见和半常见的5-MERS产生了更强的细胞反应。我们假设，负责增强免疫原性的生物过程可以用来积极地调节免疫反应，并有可能应用于疫苗开发。最初，12个罕见的5-MERS、9-MERS和13-MERS被整合到H5N1血凝素(HA)抗原的末端，并从DNA疫苗中表达。某些5聚体多肽的存在可诱导免疫应答增强。在BALB/c小鼠和雪貂中，外源性添加一种5-肽还可以改善临床结果和/或分别对抗致命性H5N1或H1N1流感病毒攻击的存活率。有趣的是，与商业乙肝疫苗(Engerix-B，GSK)相结合，在BALB/c小鼠中也观察到抗HBs Ag抗体的产生增加了25倍。从机制上讲，在体外和在NK耗竭的小鼠中，可以观察到增强多肽对NK细胞的激活和依赖性。总体而言，这些数据表明，稀有或不存在的寡肽可以被开发为免疫调节剂，并支持进一步评估一些5-聚肽作为潜在的疫苗佐剂。
Certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. Antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKB database. Experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with common-occurring sequences. We hypothesized that the biological process responsible for this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccine development. Initially, twelve rare 5-mers, 9-mers, and 13-mers were incorporated in frame at the end of an H5N1 hemagglutinin (HA) antigen and expressed from a DNA vaccine. The presence of some 5-mer peptides induced improved immune responses. Adding one 5-mer peptide exogenously also offered improved clinical outcome and/or survival against a lethal H5N1 or H1N1 influenza virus challenge in BALB/c mice and ferrets, respectively. Interestingly, enhanced anti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency was observed with enhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or non-existent oligopeptides can be developed as immunomodulators and supports the further evaluation of some 5-mer peptides as potential vaccine adjuvants.
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DOI：
10.1111/j.1749-6632.2010.05787.x
发表时间：
2010-01-01
期刊：
ANTIMICROBIAL THERAPEUTICS REVIEWS
影响因子：
--
作者：
Nicholls, Erin F.;Madera, Laurence;Hancock, Robert E. W.
通讯作者：
Hancock, Robert E. W.
影响因子：
3
作者：
Capone G;Novello G;Fasano C;Trost B;Bickis M;Kusalik A;Kanduc D
通讯作者：
Kanduc D
DOI：
10.1016/s0769-2625(87)80023-5
发表时间：
1987-09-01
期刊：
ANNALES DE L INSTITUT PASTEUR-IMMUNOLOGY
影响因子：
--
作者：
CHALUFOUR, A;BOUGUELERET, L;KOURILSKY, P
通讯作者：
KOURILSKY, P
影响因子：
4.4
作者：
Jennings, Paula;Yuan, Dorothy
通讯作者：
Yuan, Dorothy
影响因子：
5.8
作者：
Kanduc, Darja;Tessitore, Luciana;Marincola, Francesco M.
通讯作者：
Marincola, Francesco M.