Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3017, USA.
Immunol Rev. 2011 Jan;239(1):149-66. doi: 10.1111/j.1600-065X.2010.00972.x.
Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV-induced adaptive immunity to prevent reinfection, history of RSV vaccine-enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to protect infants from severe RSV disease. Therefore, the immunological goals for vaccine development are to induce effective neutralizing antibody to prevent infection and to avoid inducing T-cell response patterns associated with enhanced disease. Live-attenuated RSV and replication-competent chimeric viruses are in advanced clinical trials. Gene-based strategies, which can control the specificity and phenotypic properties of RSV-specific T-cell responses utilizing replication-defective vectors and which may improve on immunity from natural infection, are progressing through preclinical testing. Atomic level structural information on RSV envelope glycoproteins in complex with neutralizing antibodies is guiding design of new vaccine antigens that may be able to elicit RSV-specific antibody responses without induction of RSV-specific T-cell responses. These new technologies may allow development of vaccines that can protect against RSV-mediated disease in infants and establish a new immunological paradigm in the host to achieve more durable protection against reinfection.
呼吸道合胞病毒（RSV）是一种重要的呼吸道疾病病原体，可导致婴儿住院率高、儿童和成人发病率高，并导致老年人死亡率过高。疫苗开发的主要障碍包括 RSV 感染的早期年龄、RSV 逃避固有免疫的能力、RSV 诱导的适应性免疫无法预防再感染、RSV 疫苗增强疾病的历史以及缺乏完全允许人 RSV 感染的动物模型。这些生物学挑战、安全性问题和实际问题大大延长了 RSV 疫苗的开发过程。与其他困难的病毒疫苗靶点相比，一个巨大的优势是被动给予中和性单克隆抗体已知可保护婴儿免受严重 RSV 疾病的侵害。因此，疫苗开发的免疫目标是诱导有效的中和抗体以预防感染，并避免诱导与增强疾病相关的 T 细胞反应模式。减毒活 RSV 和复制型嵌合病毒正在进行临床试验。基于基因的策略可以利用复制缺陷型载体控制 RSV 特异性 T 细胞反应的特异性和表型特性，并且可能改善自然感染引起的免疫，正在进行临床前测试。与中和抗体结合的 RSV 包膜糖蛋白的原子水平结构信息指导新疫苗抗原的设计，这些新疫苗抗原可能能够在不诱导 RSV 特异性 T 细胞反应的情况下引发 RSV 特异性抗体反应。这些新技术可能使能够预防婴儿 RSV 介导疾病的疫苗的开发成为可能，并在宿主中建立新的免疫范式，以实现对再感染的更持久保护。
