Alexander J, Fikes J, Hoffman S, Franke E, Sacci J, Appella E, Chisari F V, Guidotti L G, Chesnut R W, Livingston B, Sette A
Epimmune Inc., San Diego, CA, USA.
Immunol Res. 1998;18(2):79-92. doi: 10.1007/BF02788751.
Helper T lymphocyte (HTL) responses play an important role in the induction of both humoral and cellular immune responses. Therefore, HTL epitopes are likely to be a crucial component of prophylactic and immunotherapeutic vaccines. For this reason, Pan DR helper T cell epitopes (PADRE), engineered to bind most common HLA-DR molecules with high affinity and act as powerful immunogens, were developed. Short linear peptide constructs comprising PADRE and Plasmodium-derived B cell epitopes induced antibody responses comparable to more complex multiple antigen peptides (MAP) constructs in mice. These antibody responses were composed mostly of the IgG subclass, reactive against intact sporozoites, inhibitory of schizont formation in liver invasion assays, and protective against sporozoite challenge in vivo. The PADRE HTL epitope has also been shown to augment the potency of vaccines designed to stimulate a cellular immune response. Using a HBV transgenic murine model, it was found that CTL tolerance was broken by PADRE-CTL epitope lipopeptide, but not by a similar construct containing a conventional HTL epitope. There are a number of prophylactic vaccines that are of limited efficacy, require multiple boosts, and/or confer protection to only a fraction of the immunized population. Also, in the case of virally infected or cancerous cells, new immunotherapeutic vaccines that induce strong cellular immune responses are desirable. Therefore, optimization of HTL function by use of synthetic epitopes such as PADRE or pathogen-derived, broadly crossreactive epitopes holds promise for a new generation of highly efficacious vaccines.
辅助性T淋巴细胞（HTL）反应在体液免疫和细胞免疫反应的诱导中发挥着重要作用。因此，HTL表位可能是预防性和免疫治疗性疫苗的关键组成部分。出于这个原因，人们开发了泛DR辅助性T细胞表位（PADRE），它经过工程设计，能以高亲和力结合最常见的HLA-DR分子，并作为强大的免疫原。包含PADRE和疟原虫衍生的B细胞表位的短线性肽构建体在小鼠中诱导出的抗体反应与更复杂的多抗原肽（MAP）构建体相当。这些抗体反应主要由IgG亚类组成，对完整子孢子有反应，在肝脏侵袭试验中抑制裂殖体形成，并在体内对子孢子攻击具有保护作用。PADRE HTL表位也已被证明能增强旨在刺激细胞免疫反应的疫苗的效力。使用乙肝病毒转基因小鼠模型发现，PADRE-CTL表位脂肽能打破CTL耐受性，但含有传统HTL表位的类似构建体则不能。有许多预防性疫苗疗效有限，需要多次加强免疫，和/或只能为一部分免疫人群提供保护。此外，对于病毒感染或癌细胞，需要能诱导强烈细胞免疫反应的新型免疫治疗性疫苗。因此，通过使用合成表位如PADRE或病原体衍生的广泛交叉反应表位来优化HTL功能，有望开发出新一代高效疫苗。
