T cell immunity to HIV using recombinant enteroviruses

描述（由申请人提供）：成功的HIV疫苗可能必须引起保护性T辅助、T细胞毒性和B细胞反应。目前的建议侧重于利用活的重组肠道病毒对HIV进行T细胞免疫。我们已经确定了一种肠道病毒，一种柯萨奇病毒，它是高度减毒的，但具有免疫原性。该申请涉及开发柯萨奇病毒作为艾滋病毒的疫苗载体，是一项概念验证提案。该研究的一个目标是构建柯萨奇/HIV重组体，该重组体将引发HIV特异性T辅助和T细胞毒性反应。两种策略将用于构建能够诱导两种类型T细胞反应的重组体。为了引起T辅助细胞反应，HIV多肽将在柯萨奇病毒的衣壳蛋白中表达。为了产生T细胞毒性细胞反应，HIV序列将在感染细胞中表达，但不会被合并到子代病毒粒子中。该研究的另一个目标是评估柯萨奇/HIV重组体在小鼠中的免疫原性。重组能诱导hiv特异性T辅助细胞和T细胞毒性细胞反应吗？这项研究的最终目标是确定能够增强免疫反应的参数。感染途径是否影响辅助性T细胞和T细胞毒性细胞反应的大小？细胞因子佐剂能增强T细胞免疫吗？从这项工作中获得的结果将为开发适当的重组提供框架，以便在以后的研究中在非人类灵长类动物模型中进行测试。能够引发T细胞免疫的重组体可以作为预防HIV疫苗的免疫原“鸡尾酒”的一部分。

DESCRIPTION (provided by applicant): A successful HIV vaccine will likely have to elicit protective T helper, T cytotoxic, and B cell responses. The current proposal focuses on T cell immunity to HIV using a live, recombinant enterovirus. We have identified an enterovirus, a coxsackievirus, that is highly attenuated yet immunogenic. The application addresses the development of coxsackievirus as a vaccine vector for HIV and is a proof-of-concept proposal. One goal of the study is the construction of coxsackie/HIV recombinants which will elicit HIV-specific T helper and T cytotoxic responses. Two strategies will be used to construct recombinants capable of inducing both types of T cell response. To elicit T helper cell responses, HIV peptides will be expressed within a capsid protein of coxsackievirus. To generate T cytotoxic cell responses, HIV sequences will be expressed in infected cells but will not be incorporated into progeny virions. Another goal of the study is to evaluate the immunogenicity of the coxsackie/HIV recombinants in mice. Can the recombinants induce HIV-specific T helper and T cytotoxic cell responses? The final goal of the study is to identify parameters that are able to augment the immune responses. Does the route of infection influence the magnitude of the T helper and T cytotoxic cell responses? Can T cell immunity be augmented with cytokine adjuvants? The results obtained from this work will provide the framework for developing appropriate recombinants for testing in a non-human primate model in a later study. Recombinants that can elicit T cell immunity against HIV could be part of a "cocktail" of immunogens used as a preventive HIV vaccine.