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Intramuscular delivery of replication-defective herpes simplex virus gives antigen expression in muscle syncytia and improved protection against pathogenic HSV-2 strains
Virology ( IF 2.8 ) Pub Date : 2017-10-22 , DOI: 10.1016/j.virol.2017.10.011
Fernando Diaz 1 , Sean Gregory 1 , Hiroshi Nakashima 2 , Mariano S Viapiano 2 , David M Knipe 1
Affiliation  

Herpes simplex virus 2 (HSV-2) is the leading cause of genital herpes and increases the risk of HIV infection, but there is no effective vaccine. A replication-defective HSV-2 mutant virus, dl5-29, is effective in animal models and has been in a phase I trial. Previous studies have shown that dl5-29 gives higher antibody responses and better protection when inoculated intramuscularly (IM) as compared with subcutaneously (SC). However, the basis for this effect has not been defined. We confirmed that IM inoculation of dl5-29 is more immunogenic and provides better protection than SC inoculation. IM inoculation of HSV-2 strains produced higher levels of a luciferase transgene than SC inoculation, as measured by intravital bioluminescence imaging. Intramuscular immunization also showed better protection against infection with a highly pathogenic African HSV-2, demonstrating that this single vaccine can be efficacious against HSV-2 strains from different geographic regions.



中文翻译:


肌内注射复制缺陷型单纯疱疹病毒可在肌肉合胞体中表达抗原,并改善对致病性 HSV-2 株的保护



单纯疱疹病毒 2 (HSV-2) 是生殖器疱疹的主要原因,会增加感染 HIV 的风险,但目前尚无有效的疫苗。复制缺陷型HSV-2突变病毒dl 5-29在动物模型中有效,并已进入I期试验。先前的研究表明,与皮下注射 (SC) 相比,肌肉注射 (IM) 接种时, dl 5-29 可以提供更高的抗体反应和更好的保护。然而,这种效应的基础尚未确定。我们证实,IM 接种dl 5-29 比 SC 接种更具免疫原性并提供更好的保护。根据活体生物发光成像测量,HSV-2 菌株的 IM 接种比 SC 接种产生更高水平的荧光素酶转基因。肌内免疫还显示出更好的预防高致病性非洲 HSV-2 感染的保护作用,表明这种单一疫苗可以有效对抗来自不同地理区域的 HSV-2 毒株。

更新日期:2017-10-22
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