Folgori Antonella, Capone Stefania, Ruggeri Lionello, Meola Annalisa, Sporeno Elisabetta, Ercole Bruno Bruni, Pezzanera Monica, Tafi Rosalba, Arcuri Mirko, Fattori Elena, Lahm Armin, Luzzago Alessandra, Vitelli Alessandra, Colloca Stefano, Cortese Riccardo, Nicosia Alfredo
Istituto di Ricerche di Biologia Molecolare P. Angeletti, via Pontina km30,600, 00040 Pomezia, Rome, Italy.
Nat Med. 2006 Feb;12(2):190-7. doi: 10.1038/nm1353. Epub 2006 Feb 5.
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.
全球3%的人口长期感染丙型肝炎病毒(HCV),并有患肝癌的风险。有效的细胞免疫反应被认为是急性丙型肝炎自然痊愈和长期保护的关键。在此,我们描述了一种新型T细胞HCV基因疫苗,它能够保护黑猩猩免受异源病毒攻击诱导的急性肝炎。接种疫苗的黑猩猩体内急性病毒血症受到抑制,这是外周和肝内HCV特异性CD8(+) T淋巴细胞大量扩增的结果,这些细胞与疫苗和病毒表位发生交叉反应。这些发现表明,仅通过刺激免疫系统的细胞部分就有可能引发针对异源HCV毒株的有效免疫反应,并为针对像HCV、HIV或疟疾这类高度可变且能逃避体液反应的人类病原体的新型免疫疗法指明了道路。