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用于人类疫苗的呼吸道合胞病毒(RSV)减毒活疫苗空斑纯化毒株的免疫学特性

Immunological properties of plaque purified strains of live attenuated respiratory syncytial virus (RSV) for human vaccine.

作者信息

Herlocher M L, Ewasyshyn M, Sambhara S, Gharaee-Kermani M, Cho D, Lai J, Klein M, Maassab H F

机构信息

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor 48109-2029, USA.

出版信息

Vaccine. 1999 Jan;17(2):172-81. doi: 10.1016/s0264-410x(98)00155-8.

Abstract

Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in infants, young children, and the elderly. Efforts to develop satisfactory live or inactivated vaccines have not yet been proven successful. Our research focuses on the development of four purified live attenuated RSV sub-type A human vaccine clones. Temperature sensitive (ts) and attenuated purified clones of either cold-adapted (ca) RSV or high-passage (hp) RSV were administered intra-nasally (i.n.) to BALB/c mice and tested for immunogenicity. All four clones produced significant anti-RSV F IgG2a and IgG1 titres in the sera of mice, RSV-specific neutralizing titres higher than those produced by their wild-type progenitor viruses, cytotoxic T-lymphocyte (CTL) activity, and total protection against wild-type (wt) viral challenge. These purified vaccine candidates await testing in humans to determine which contain the required balance between immunogenicity and attenuation.

摘要

呼吸道合胞病毒(RSV)可导致婴儿、幼儿和老年人发生严重的下呼吸道疾病。开发令人满意的减毒活疫苗或灭活疫苗的努力尚未被证明是成功的。我们的研究重点是开发四种纯化的减毒活RSV A型人疫苗克隆株。将温度敏感(ts)以及冷适应(ca)RSV或高传代(hp)RSV的减毒纯化克隆株经鼻内(i.n.)接种给BALB/c小鼠,并检测其免疫原性。所有这四种克隆株均在小鼠血清中产生了显著的抗RSV F IgG2a和IgG1滴度、高于其野生型亲代病毒产生的RSV特异性中和滴度、细胞毒性T淋巴细胞(CTL)活性,并且对野生型(wt)病毒攻击具有完全保护作用。这些纯化的候选疫苗有待在人体中进行测试,以确定哪些疫苗在免疫原性和减毒之间达到了所需的平衡。

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