A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees
A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees
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DOI：
10.1038/nm1353
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发表时间：
2006-02-01
期刊：
影响因子：
82.9
通讯作者：
Nicosia, A
中科院分区：
文献类型：
--
作者：
Folgori, A;Capone, S;Nicosia, A
世界上百分之三的人口慢性感染丙型肝炎病毒（HCV），并有患肝癌的风险。有效的细胞免疫应答被认为是急性丙型肝炎自发消退和长期保护的关键。在这里，我们描述了一种新的T细胞HCV基因疫苗，能够保护黑猩猩免受由异源病毒攻击引起的急性肝炎。接种疫苗的黑猩猩中急性病毒血症的抑制是由于外周和肝内HCV特异性CD8（+）T淋巴细胞与疫苗和病毒表位交叉反应的大量扩增。这些发现表明，通过仅刺激免疫系统的细胞臂，可以引起对异源HCV毒株的有效免疫，并提出了针对高度可变的人类病原体如HCV，HIV或疟疾的新免疫疗法的途径，这些病原体可以逃避体液应答。
Three percent of the world's population is chronically infected with the hepatitis C virus (HCV) and at risk of developing liver cancer. Effective cellular immune responses are deemed essential for spontaneous resolution of acute hepatitis C and long-term protection. Here we describe a new T-cell HCV genetic vaccine capable of protecting chimpanzees from acute hepatitis induced by challenge with heterologous virus. Suppression of acute viremia in vaccinated chimpanzees occurred as a result of massive expansion of peripheral and intrahepatic HCV-specific CD8(+) T lymphocytes that cross-reacted with vaccine and virus epitopes. These findings show that it is possible to elicit effective immunity against heterologous HCV strains by stimulating only the cellular arm of the immune system, and suggest a path for new immunotherapy against highly variable human pathogens like HCV, HIV or malaria, which can evade humoral responses.