Evaluation of AD472, a live attenuated recombinant herpes simplex virus type 2 vaccine in guinea pigs.
Evaluation of AD472, a live attenuated recombinant herpes simplex virus type 2 vaccine in guinea pigs.
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DOI：
10.1016/j.vaccine.2005.02.028
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发表时间：
2005-11
期刊：
影响因子：
5.5
通讯作者：
M. Prichard;R. Kaiwar;W. T. Jackman;D. Quenelle;Deborah J. Collins;E. Kern;G. Kemble;R. Spaete
中科院分区：
文献类型：
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作者：
M. Prichard;R. Kaiwar;W. T. Jackman;D. Quenelle;Deborah J. Collins;E. Kern;G. Kemble;R. Spaete
从单纯疱疹病毒2型（HSV-2）G株中删除γ134.5基因UL 55 -56、UL43.5和US 10 -12区，构建了一株减毒的重组HSV-2，命名为AD 472。该病毒被改造成安全有效的减毒HSV-2活疫苗，并在生殖器疱疹豚鼠模型中进行测试，以评估其在用野生型（wt）病毒HSV-2（G）攻击时保护免于疾病的能力。肌内给予AD 472不能预防阴道中的感染或病毒复制，但在用wt病毒攻击的豚鼠中确实以剂量依赖性方式减少病变发展和严重程度。与亲本病毒HSV-2（G）相比，潜伏期再激活的频率较低。以1× 105 PFU的剂量接种AD 472通常可排除攻击病毒在神经节的定殖或潜伏期的建立。这里提出的结果支持的概念，一个合理的工程活减毒疫苗的生殖器疾病的预防与HSV-2感染。
An attenuated recombinant herpes simplex virus type 2 (HSV-2), designated as AD472, was constructed by deleting both copies of the γ134.5 gene, UL55-56, UL43.5, and the US10–12 region from HSV-2 strain G. This virus was engineered to be a safe and effective live attenuated HSV-2 vaccine and was tested in the guinea pig model of genital herpes to evaluate its ability to protect from disease upon challenge with the wild type (wt) virus, HSV-2 (G). AD472 administered intramuscularly did not prevent infection or virus replication in the vaginal tract, but did reduce both lesion development and severity in a dose-dependent manner in guinea pigs challenged with the wt virus. Frequency of reactivation from latency was low compared with that of the parent virus, HSV-2 (G). Immunization with AD472 at doses of 1×105PFU generally precluded colonization of the ganglia or establishment of latency by the challenge virus. Results presented here support the concept of a rationally engineered live attenuated vaccine for the prevention of the genital disease associated with infection by HSV-2.