HIV vaccine development using recombinant coxsackieviruses

迄今为止，没有一种疫苗策略能够引发被认为是免疫反应的整个免疫反应谱。 有效的艾滋病毒疫苗。这项研究的长期目标是开发一个新的平台， 使用靶向表位策略创建重组疫苗，能够诱导多种HIV特异性 免疫反应。总的假设是，在适当的条件下，靶向HIV表位的表达可能与靶向HIV表位的表达有关。 在免疫学背景下，将引发广泛的免疫应答。靶向表位的优势 策略是在HIV疫苗中表达结构受限、保守的免疫原性肽 能最大限度地减少逃跑变种人的问题这项研究与艾滋病毒疫苗有关，因为它 描述了原理验证实验，以解决疫苗开发中的两个关键问题，即 不同的免疫反应和逃逸突变体的发展。该提案的重点是1） 诱导gag p24特异性T辅助细胞应答的CVB 4/HIV重组体的构建，2）构建 CVB 4/HIV重组体的构建 诱导病毒中和抗体的重组体，和4）评估重组体的混合物的免疫原性， 通过口服或鼻内途径给予CVB 4/HIV重组体。重组体的免疫原性 表达T辅助细胞表位的细胞将使用T细胞增殖测定和ELISPOT 比色法表达CTL表位的重组体的免疫原性将使用ELISPOT进行监测。 比色法表达B细胞表位的重组体的免疫原性将通过ELISA和免疫组织化学法评估。 病毒中和测定。在每种类别中诱导最强免疫反应的免疫剂将 被分组制成疫苗鸡尾酒。将测试几种佐剂以鉴定增强免疫应答的佐剂。 鸡尾酒疫苗诱导的HIV特异性免疫反应的广度和强度。涉及 公共卫生：迫切需要一种预防性疫苗来阻止HIV-1的全球传播。当前疫苗 候选物是有希望的，因为它们能够诱导一些必要的免疫应答。新 需要疫苗策略来增加免疫应答的库，并克服免疫应答的缺陷。 逃避突变体的问题目前的建议描述了一种新的方法，以增加艾滋病毒的具体 免疫反应，并尽量减少逃逸突变体的问题。

To date, no single vaccine strategy is capable of eliciting the entire spectrum of immune responses deemed necessary for an effective HIV vaccine. The long-term goal of this study is to develop a new platform for creating recombinant vaccines, using a targeted epitope strategy, capable of inducing diverse HIV-specific immune responses. The overall hypothesis is that expression of targeted HIV epitopes, in appropriate immunological contexts, will elicit a wide range of immune responses. The advantage of a targeted epitope strategy is that expression of structurally constrained, conserved, immunogenic peptides in an HIV vaccine will minimize the problem of escape mutants. The proposed study is relevant for HIV vaccines because it describes proof-of-principle experiments to address two critical issues in vaccine development i.e.the need for diverse immune responses and the development of escape mutants. The proposal focuses on 1) Construction of CVB4/HIV recombinants that elicit gag p24-specific T helper cell responses, 2) Construction of a CVB4/HIV recombinant that elicits gag p24-specific CTL responses, 3) Construction of CVB4/HIV recombinants that elicit virus neutralizing antibodies, and 4) Evaluation of the immunogenicity of a cocktail of CVB4/HIV recombinants administered via the oral or intranasal route. The immunogenicity of recombinants expressing T helper cell epitopes will be evaluated using a T cell proliferation assay and the ELISPOT assay. The immunogenicity of recombinants expressing CTL epitopes will be monitored using the ELISPOT assay. The immunogenicity of recombinants expressing B cell epitopes will be assessed by ELISA and by a virus-neutralization assay. Recombinants that induce the strongest immune response in each category will be grouped to make a vaccine cocktail. Several adjuvants will be tested to identify adjuvants that enhance the breadth and strength of HIV-specific immune responses induced by the vaccine cocktail. Relevance to public health: A preventive vaccine is urgently needed to halt the global spread of HIV-1. Current vaccine candidates are promising in that they are able to induce some of the necessary immune responses. New vaccine strategies are needed to increase the repertoire of immune responses and to overcome the problem of escape mutants. The present proposal describes a new approach to augment HIV-specific immune responses and to minimize the problem of escape mutants.