Takimoto Toru, Hurwitz Julia L, Zhan Xiaoyan, Krishnamurthy Sateesh, Prouser Cecilia, Brown Brita, Coleclough Chris, Boyd Kelli, Scroggs Ruth A, Portner Allen, Slobod Karen S
Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
Viral Immunol. 2005;18(2):255-66. doi: 10.1089/vim.2005.18.255.
Respiratory syncytial virus (RSV) is among the most important and serious pediatric respiratory diseases, and yet after more than four decades of research an effective vaccine is still unavailable. This review examines the role of the immune response in reducing disease severity; considers the history of RSV vaccine development; and advocates the potential utility of Sendai virus (a murine paramyxovirus) as a xenogenic vaccine vector for the delivery of RSV antigens. The immunogenicity and protective efficacy of RSV-recombinant Sendai virus vectors constructed using reverse genetics is examined. RSV-recombinant Sendai virus is easy to grow (i.e., achieves extremely high titers in eggs), is easy to administer (intranasal drops), and elicits both B- and T-cell responses leading to protection from RSV challenge in a small-animal model. Unmodified Sendai virus is currently being studied in clinical trials as a vaccine for its closely related human cognate (human parainfluenza virus type 1). Sendai virus may prove an enormously valuable vaccine platform, permitting the delivery of recombinants targeting important pediatric respiratory pathogens, RSV chief among them.
呼吸道合胞病毒(RSV)是最重要且最严重的儿科呼吸道疾病之一,然而经过四十多年的研究,仍未研发出有效的疫苗。本综述探讨了免疫反应在降低疾病严重程度方面的作用;回顾了RSV疫苗的研发历程;并提倡将仙台病毒(一种鼠源副粘病毒)作为一种异源疫苗载体来递送RSV抗原的潜在效用。研究了利用反向遗传学构建的RSV重组仙台病毒载体的免疫原性和保护效力。RSV重组仙台病毒易于培养(即在鸡胚中能达到极高滴度),易于给药(滴鼻),并能引发B细胞和T细胞反应,从而在小动物模型中对RSV攻击产生保护作用。未修饰的仙台病毒目前正在作为其密切相关的人类同源病毒(1型人副流感病毒)的疫苗进行临床试验研究。仙台病毒可能被证明是一个极具价值的疫苗平台,可用于递送针对重要儿科呼吸道病原体的重组体,其中RSV最为主要。