Live subgroup B respiratory syncytial virus vaccines that are attenuated, genetically stable, and immunogenic in rodents and nonhuman primates
Live subgroup B respiratory syncytial virus vaccines that are attenuated, genetically stable, and immunogenic in rodents and nonhuman primates
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DOI：
10.1093/infdis/173.4.829
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发表时间：
1996-04-01
影响因子：
6.4
通讯作者：
Murphy, BR
中科院分区：
文献类型：
--
作者：
Crowe, JE;Bui, PT;Murphy, BR
新生儿针对呼吸道合胞病毒（RSV）引起的疾病的最佳免疫可能需要多次接种含有A亚组和B亚组病毒的疫苗，产生了含有多种减毒突变的活亚组B RSV突变体，ts（温度敏感）和非温度敏感（宿主范围），通过在细胞培养物中延长传代或通过化学诱变引入，与野生型病毒相比，冷传代（cp）-52突变体在啮齿动物和非人灵长类动物中的复制受到限制。此外，cp-52的减毒表型在免疫抑制的啮齿动物中延长复制后是稳定的，然后将一个或两个ts突变引入cp-52突变体中以产生比cp-52亲本病毒在体内更减毒的另外的候选疫苗株。正在进行人体试验以确定一种或多种RSV B-1突变体是否在减毒和免疫原性之间表现出令人满意的平衡。
Optimal immunization of neonates against disease caused by respiratory syncytial virus (RSV) probably will require multiple doses of a vaccine containing viruses of both subgroups A and B, Live subgroup B RSV mutants were generated containing multiple attenuating mutations, ts (temperature-sensitive) and non-ts (host range), that were introduced by prolonged passage in cell culture or by chemical mutagenesis, The cold-passaged (cp)-52 mutant was restricted in replication compared to wild type virus in rodents and nonhuman primates, In addition, the attenuation phenotype of cp-52 was stable after prolonged replication in immunosuppressed rodents, One or two ts mutations were then introduced into the cp-52 mutant to generate additional candidate vaccine strains that were more attenuated in vivo than the cp-52 parental virus, Tests in humans are being done to determine if one or more of the RSV B-1 mutants exhibit a satisfactory balance between attenuation and immunogenicity.