Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA, USA.
Immunol Rev. 2011 Nov;244(1):149-68. doi: 10.1111/j.1600-065X.2011.01062.x.
The human respiratory tract is an entry point for over 200 known viruses that collectively contribute to millions of annual deaths worldwide. Consequently, the World Health Organization has designated respiratory viral infections as a priority for vaccine development. Despite enormous advances in understanding the attributes of a protective mucosal antiviral immune response, current vaccines continue to fail in effectively generating long-lived protective CD8(+) T-cell immunity. To date, the majority of licensed human vaccines afford protection against infectious pathogens through the generation of specific immunoglobulin responses. In recent years, the selective manipulation of specific costimulatory pathways, which are critical in regulating T cell-mediated immune responses, has generated increasing interest. Impressive results in animal models have shown that the tumor necrosis factor receptor (TNFR) family member OX40 (CD134) and its binding partner OX40L (CD252) are key costimulatory molecules involved in the generation of protective CD8(+) T-cell responses at mucosal surfaces, such as the lung. In this review, we highlight these new findings with a particular emphasis on their potential as immunological adjuvants to enhance poxvirus-based CD8(+) T-cell vaccines.
人类呼吸道是 200 多种已知病毒的进入点，这些病毒共同导致了全球每年数百万人的死亡。因此，世界卫生组织已将呼吸道病毒感染列为疫苗开发的优先事项。尽管在理解保护性黏膜抗病毒免疫反应的特性方面取得了巨大进展，但目前的疫苗仍未能有效产生持久的保护性 CD8+T 细胞免疫。迄今为止，大多数已批准的人类疫苗通过产生特异性免疫球蛋白反应来提供针对传染病原体的保护。近年来，对调节 T 细胞介导的免疫反应至关重要的特定共刺激途径的选择性操纵引起了越来越多的关注。动物模型中的令人印象深刻的结果表明，肿瘤坏死因子受体（TNFR）家族成员 OX40（CD134）及其结合伴侣 OX40L（CD252）是参与在肺部等黏膜表面产生保护性 CD8+T 细胞反应的关键共刺激分子。在这篇综述中，我们重点介绍了这些新发现，特别强调了它们作为增强基于痘病毒的 CD8+T 细胞疫苗的免疫佐剂的潜力。
