ENHANCING IMMUNOGENICITY OF EPITOPE INSERTS IN FLAGELLIN

1.已经证明鞭毛蛋白的高变区 沙门氏菌菌株(可能用作伤寒疫苗)是一种 适合插入编码下列表位的DNA的基因座 兴趣是治疗其他疾病的潜在有效免疫原 沙门氏菌病。代表IL-1β的163-171氨基酸的九肽 已被证明具有增强免疫力的作用。我们将测试表达式是否 增强了对决定因素的免疫应答 与该九肽并列、接近或在空间上远离该九肽 插入沙门氏菌疫苗株的高变区。 2.许多多糖类抗原被认为是BC-T非依赖的 感觉到对它们的反应不需要T细胞的帮助；记忆 不会引起反应，免疫球蛋白同型反应是 受这种抗原限制的。我们建议测试一种方法来转换 这些抗原的寡糖决定因素对T依赖性使能 既有记忆的启发，又有无限制的类切换。 此外，这一过程将使获得这样的抗原成为可能 以多肽替代品的形式表达为背负抗原 鞭毛蛋白高变区1.抗沙门氏菌的单抗 VI将用于筛选不定芽的随机多肽文库 将被反向翻译成DNA的交叉反应多肽，以及 插入以在鞭毛蛋白的高变区表达。这个 基本假设是在反应中识别的交叉反应 会不会与BC的交叉反应相匹配，诱导免疫应答。 具体地说，这可能会大大增强伤寒的效用。 疫苗正在进行测试，因为它们目前不会引发抗Vi。

1. It has been shown that the hypervariable region of flagellin of strains of Salmonella (potentially useful as typhoid vaccines) is a suitable locus for insertion of DNA coding for epitopes which are of interest as potentially effective immunogens for diseases other than salmonellosis. A nonapeptide which represents aa163-171 of Il-1 beta has been shown to be immunoenhancing. We shall test whether the expression of this nonapeptide enhances immune response to determinants which are juxtaposed to, near or spatially removed from this nonapeptide when it is inserted in the hypervariable region of vaccine strains of Salmonella. 2. Many polysaccharide antigens are considered to bc T independent in the sense that response to them does not require T cell help; anamnestic responses are not elicited and the immunoglobulin isotype response is restricted with such antigens. We propose to test a method to convert oligosaccharide determinants of such antigens to T dependence enabling both the elicitation of memory and unrestricted class switching. Furthermore, the process would make it possible to have such antigens expressed as peptide surrogates as piggy-back antigens in the hypervariable region of flagellin as in 1. A monoclonal anti Salmonella Vi will be used to screen a random peptide library for adventitious cross-reactive peptides which will be back-translated to DNA, and inserted for expression in the hypervariable region of flagellin. The essential hypothesis is that cross-reactivity as recognized in reaction will bc matched by cross-reactivity in induction of immune response. Specifically this might greatly enhance the utility of the typhoid vaccines being tested since they do not at present elicit anti-Vi.