生物谷报道：科学家研发了一种丙型肝炎疫苗，它可以引发黑猩猩的免疫应答。
丙肝病毒是通过被污染的血液传播的。感染可以导致永久性的肝损伤，慢性肝感染和肝衰竭。目前尚无丙肝疫苗，而治疗丙肝超过了发展中国家绝大多数人的承受能力——每月花费1600美元到2300美元，疗程持续6到12个月。
如今，美国国立卫生研究院的科学家证明了一种类似于丙肝病毒一部分的分子构成的候选疫苗可以引发动物对这种病毒的免疫应答。作为一种候选疫苗，这具有一定吸引力，因为它可以引发免疫应答，但是不会导致感染。
此前用类似病毒的颗粒制造丙肝疫苗的努力只取得了防止感染的部分效果。
给4只黑猩猩接种这种候选疫苗后，它们体内产生了可以检测到的免疫应答，持续了至少6个月。当给它们注射丙肝病毒之后，它们迅速控制了感染。
相比之下，4只未接种疫苗的黑猩猩中的3只在注射丙肝病毒后被长期感染了。
这组科学家还发现接种疫苗的黑猩猩体内的病毒水平是对照组的1/5到1/10，这证明了这种疫苗的效果。
然而接种疫苗的黑猩猩的免疫应答仍然很弱。根据该研究的负责人T. Jake Liang，下一阶段的研究将通过转基因的方法提高免疫系统对丙肝病毒的应答，从而改善这种候选疫苗的效果。
美国Morehouse医学院的尼日利亚裔科学家Daniel Okenu对这项新进展表示了欢迎。他告诉本网站说这样一种疫苗将造福发展中国家，因为发展中国家只有有限的资源用于昂贵的丙肝治疗体制。
然而，他对于专利管制是否允许发展中国家获取这项技术表示怀疑。世界卫生组织估计，约1.7亿丙肝感染者中的大部分生活在发展中国家。Okenu强调了鼓励在各地方以适中的价格生产这类疫苗的必要性。
这项研究发表在了上周（5月7日）的《美国科学院学报》上。
原始出处:
Published online before print May 7, 2007, 10.1073/pnas.0702162104
PNAS | May 15, 2007 | vol. 104 | no. 20 | 8427-8432
BIOLOGICAL SCIENCES / MEDICAL SCIENCES
A functional SNP of interferon- gene is important for interferon--induced and spontaneous recovery from hepatitis C virus infection
Ying Huang*, Huiying Yang, Brian B. Borg*, Xiaowen Su, Shannon L. Rhodes, Kai Yang, Xiaomei Tong, George Tang, Charles D. Howell, Hugo R. Rosen, Chloe L. Thio¶, David L. Thomas¶, Harvey J. Alter||,**, Ronda K. Sapp*, and T. Jake Liang*,
*Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048; University of Maryland School of Medicine, Baltimore, MD 21201; Division of Gastroenterology/Hepatology, University of Colorado Health Sciences Center, Denver, CO 80262; ¶Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231; and ||Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD 20892
Contributed by Harvey J. Alter, November 13, 2006 (received for review October 10, 2006)
Abstract
Cytokine polymorphisms are associated with disease outcome and interferon (IFN) treatment response in hepatitis C virus (HCV) infection. We genotyped eight SNPs spanning the entire IFN- gene in two cohorts and assessed the association between those polymorphisms and treatment response or spontaneous viral clearance. The first cohort was composed of 284 chronically HCV-infected patients who had received IFN--based therapy and the second was 251 i.v. drug users who had either spontaneously cleared HCV or become chronically infected. A SNP variant located in the proximal IFN- promoter region next to the binding motif of heat shock transcription factor (HSF), –764G, was significantly associated with sustained virological response [P = 0.04, odds ratio (OR) = 3.51 (confidence interval 1.0–12.5)]. The association was independently significant in multiple logistic regression (P = 0.04) along with race, viral titer, and genotype. This variant was also significantly associated with spontaneous recovery [P = 0.04, OR = 3.51 (1.0–12.5)] in the second cohort. Functional analyses show that the G allele confers a two- to three-fold higher promoter activity and stronger binding affinity to HSF1 than the C allele. Our study suggests that the IFN- promoter SNP –764G/C is functionally important in determining viral clearance and treatment response in HCV-infected patients and may be used as a genetic marker to predict sustained virological response in HCV-infected patients.
genetics | human study | cytokine | viral clearance | antiviral treatment
相关研究进展:
首次有证据显示丙肝疫苗可能被研究出来
加拿大科学家研制出新型抗丙肝病毒疫苗
美国研究人员称开发出新型“丙型肝炎疫苗”
《Science》：帮助丙肝病毒免疫的基因型
国内第一个治丙肝新中药日前获准投放临床
我国首个丙肝抗原诊断试剂问世
PNAS：甲肝和丙肝病毒攻击同一个蛋白质
YF17D可作为新型疫苗和基因治疗病毒载体
