生物谷報(bào)道：科學(xué)家研發(fā)了一種丙型肝炎疫苗,，它可以引發(fā)黑猩猩的免疫應(yīng)答。
丙肝病毒是通過被污染的血液傳播的,。感染可以導(dǎo)致永久性的肝損傷,，慢性肝感染和肝衰竭。目前尚無丙肝疫苗,，而治療丙肝超過了發(fā)展中國家絕大多數(shù)人的承受能力——每月花費(fèi)1600美元到2300美元,，療程持續(xù)6到12個月。
如今,，美國國立衛(wèi)生研究院的科學(xué)家證明了一種類似于丙肝病毒一部分的分子構(gòu)成的候選疫苗可以引發(fā)動物對這種病毒的免疫應(yīng)答,。作為一種候選疫苗，這具有一定吸引力,，因?yàn)樗梢砸l(fā)免疫應(yīng)答,，但是不會導(dǎo)致感染。
此前用類似病毒的顆粒制造丙肝疫苗的努力只取得了防止感染的部分效果,。
給4只黑猩猩接種這種候選疫苗后,，它們體內(nèi)產(chǎn)生了可以檢測到的免疫應(yīng)答，持續(xù)了至少6個月,。當(dāng)給它們注射丙肝病毒之后,，它們迅速控制了感染。
相比之下,，4只未接種疫苗的黑猩猩中的3只在注射丙肝病毒后被長期感染了,。
這組科學(xué)家還發(fā)現(xiàn)接種疫苗的黑猩猩體內(nèi)的病毒水平是對照組的1/5到1/10，這證明了這種疫苗的效果,。
然而接種疫苗的黑猩猩的免疫應(yīng)答仍然很弱,。根據(jù)該研究的負(fù)責(zé)人T. Jake Liang，下一階段的研究將通過轉(zhuǎn)基因的方法提高免疫系統(tǒng)對丙肝病毒的應(yīng)答,，從而改善這種候選疫苗的效果,。
美國Morehouse醫(yī)學(xué)院的尼日利亞裔科學(xué)家Daniel Okenu對這項(xiàng)新進(jìn)展表示了歡迎。他告訴本網(wǎng)站說這樣一種疫苗將造福發(fā)展中國家,，因?yàn)榘l(fā)展中國家只有有限的資源用于昂貴的丙肝治療體制,。
然而，他對于專利管制是否允許發(fā)展中國家獲取這項(xiàng)技術(shù)表示懷疑,。世界衛(wèi)生組織估計(jì),，約1.7億丙肝感染者中的大部分生活在發(fā)展中國家。Okenu強(qiáng)調(diào)了鼓勵在各地方以適中的價(jià)格生產(chǎn)這類疫苗的必要性,。
這項(xiàng)研究發(fā)表在了上周（5月7日）的《美國科學(xué)院學(xué)報(bào)》上,。
原始出處:
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
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