Design and Testing of a Parechovirus Vaccine Vector

描述(由申请人提供)：诱导粘膜免疫反应将是成功阻断艾滋病毒感染传播的疫苗的基本属性。在SIV动物模型系统中的研究表明，黏膜暴露于病毒载体和多肽后的免疫反应可以钝化SIV感染后的复制和发病。基于脊髓灰质炎病毒和柯萨奇病毒两个成员的病毒载体已被用于其中一些研究。使用这些和类似的肠道病毒很有吸引力，因为它们在下胃肠道复制，并可能在胃肠道和生殖道产生免疫反应。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挫伤将这些特定病毒用作疫苗载体的热情。细小核糖核酸病毒与柯萨奇病毒和脊髓灰质炎病毒株密切相关，但在生物学上截然不同，与迄今使用的柯萨奇和脊髓灰质炎病毒株相比，这些病毒似乎自然减毒。尤其重要的是，细小病毒的严重并发症很少有报道，即使在婴儿感染之后也是如此。基于已成功构建肠道病毒载体的策略，我们建议构建并完成基于副病毒的疫苗载体的初步体外测试。

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.