Combined TLR/CD40-agonist vaccine

描述（由申请人提供）：在针对天然感染的免疫应答的峰值，宿主可以产生病原体特异性T细胞应答，其占宿主总T细胞库的20-50%。我们现在已经确定了一种疫苗接种策略，该策略能够从纯分子疫苗产生类似水平的T细胞扩增，这是先前开发的疫苗策略不可能实现的结果。这些高水平的CD 8 + T细胞扩增可以通过用抗原与Toll样受体（TLR）和CD 40途径两者的激动剂组合接种宿主（组合TLR/CD 40激动剂免疫）来实现。重要的是，我们还确定了这种疫苗的成功，即使在CD 4缺陷型宿主中也能成功产生原发性和记忆性CD 8 + T细胞应答。这是该疫苗接种方法独有的特征（与其他公开的方法相比），并且是疫苗接种成功治疗其中CD 4 T细胞功能严重受损的HIV感染个体的必要组成部分。到目前为止，使用这种疫苗接种技术进行的所有研究都需要分别注射抗原、TLR激动剂和CD 40激动剂;这构成了将这种疫苗接种方法推广到临床环境的复杂性。为了简化疫苗生产和临床应用，我们将生产一种疫苗，其中所有三种组分都包含在一个单一的分子实体中;即。TLR/CD 40激动剂结合疫苗。疫苗生产后，我们将评价针对全身和粘膜病毒攻击的保护性免疫的诱导。这些可能是成功的疫苗的必要组成部分，用于对抗通过生殖器粘膜传播后产生全身感染的病毒（如HIV）。这些研究将导致一种新的疫苗接种策略的发展，能够诱导有效的细胞免疫，并持有显着的承诺，快速人源化和调查的预防和/或治疗艾滋病毒的疗效。

DESCRIPTION (provided by applicant): At the peak of an immune responses against a natural infection, a host can generate pathogen-specific T cell responses that comprise 20-50% of the hosts total T cell pool. We have now identified a vaccination strategy that is able to generate a similar level of T cell expansion from a purely molecular based vaccine, a result not possible with previously developed vaccine strategies. These high levels of CD8+ T cell expansion can be achieved by the vaccination of a host with antigen in combination with agonists for both the Toll-Like Receptor (TLR) and CD40 pathways (combined TLR/CD40-agonist immunization). Importantly, we have also determined the success of this vaccine successfully generating primary and memory CD8+ T cell responses even in CD4 deficient hosts. This is a feature unique to this vaccination method (in comparison to other published methods) and is a necessary component for a vaccination to be successful in treating HIV infected individuals where CD4 T cell function is so heavily compromised. All studies conducted up until now using this vaccination technique have required the separate injection of the antigen, the TLR agonist, and the CD40 agonist; this constitutes a complication in the effort to move this vaccination method into a clinical setting. For the purpose of simplifying vaccine production and clinical implementation, we will producing a vaccine in which all three components were contained within a single molecular entity; ie. a combined TLR/CD40-agonist conjugate vaccine. Following production of the vaccine, we will evaluate the induction of protective immunity against both systemic and mucosal viral challenge. These are likely necessary components of a successful vaccine against a virus such as HIV which produces a systemic infection following transmission via the genital mucosa. These studies will result in the development of a novel vaccination strategy capable of inducing potent cellular immunity and which holds significant promise for rapid humanization and investigation for prophylactic and/or therapeutic efficacy against HIV.