Design and Testing of a Parechovirus Vaccine Vector

描述（由申请方提供）：诱导粘膜免疫应答将是成功阻断HIV感染传播的疫苗的基本属性。在SIV动物模型系统中的研究已经证明，粘膜暴露于病毒载体和肽后的免疫应答可以减弱SIV感染后的复制和致病性。基于脊髓灰质炎病毒和柯萨奇病毒的两个成员的病毒载体已被用于这些研究中的一些。这些和类似的肠道病毒的使用是有吸引力的，因为它们在下胃肠道中复制，并且可能在胃肠道和生殖道中产生免疫应答。然而，安全问题和完全遏制脊髓灰质炎病毒传播的计划可能会抑制使用这些特定病毒作为疫苗载体的热情。双埃柯病毒是密切相关的，但生物学上不同的小核糖核酸病毒，相对于迄今为止使用科萨基和脊髓灰质炎病毒株，它们似乎是天然减毒的。特别重要的是，双埃柯病毒的严重并发症很少报告，即使在婴儿感染后也是如此。我们建议构建并完成基于双埃柯病毒的疫苗载体的初步体外测试，基于已成功构建肠道病毒载体的策略。

DESCRIPTION (provided by applicant): Induction of a mucosal immune response will be an essential attribute of a successful vaccine to block transmission of HIV infection. Studies in the SIV animal model system have demonstrated that immune responses following mucosal exposure to viral vectors and peptides can blunt the replication and pathogenesis of SIV after infection. Viral vectors based on two members of the poliovirus and coxsackievirus have been employed in some of these studies. The use of these and similar enteroviruses is attractive, as they replicate in lower gastrointestinal tract, and are likely to produce immune responses in both the gastrointestinal and genital tracts. However, safety concerns and plans to completely curtail the circulation of poliovirus are likely to dampen enthusiasm for using these specific viruses as vaccine vectors. The parechoviruses are closely related, but biologically distinct picornaviruses that appear naturally attenuated relative to coxsackie and polioviruses strains employed to date. Of particular importance, serious complications of parechovirus have been only rarely reported, even after infection of infants. We propose to construct and complete the initial in vitro testing of a parechovirus based vaccine vector, based on strategies already employed in the successful construction of enteroviral vectors.