日前，發(fā)表在Sci Transl Med雜志上的一項研究報告"Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man"披露,，黑猩猩的腺病毒可被用來制造疫苗,。
研究結(jié)果提示，用黑猩猩載體所研發(fā)的疫苗可觸發(fā)對C型肝炎的免疫保護(hù),；引起C型肝炎的病毒預(yù)計造成全球1億7000萬人的感染,；目前還沒有針對該病的疫苗。 人類腺病毒常被用作載體將基因帶進(jìn)人的細(xì)胞之中以遞送疫苗或進(jìn)行基因療法,。 在疫苗中,，那些編碼某種特別病原體抗原的基因被包裝到該病毒之中。一旦這些抗原被釋放到細(xì)胞之內(nèi),，它們會觸發(fā)一種保護(hù)性的免疫反應(yīng),。 但是最近的研究表明，人類的腺病毒可能不是最好的疫苗載體,，因為許多人群過去曾經(jīng)接觸過這些病毒,。 這種預(yù)先存在的免疫力會在該病毒刺激某種新的免疫反應(yīng)之前就遭到清除。
考慮到大多數(shù)人從黑猩猩那里感染微生物的可能性要小的多,，因此研究人員轉(zhuǎn)而考慮用黑猩猩的腺病毒來作為潛在的疫苗載體,。Stefano Colloca及其同事在一項試驗中發(fā)現(xiàn)了一組新的黑猩猩腺病毒，并設(shè)計了一種篩檢的策略來對其在小鼠中的免疫強度（即檢測它們作為疫苗載體的有效性）進(jìn)行排序,。該團(tuán)隊證明,，黑猩猩腺病毒比大多數(shù)的人類腺病毒效果更好。在一項獨立的臨床一期試驗中,，Eleanor Barnes及其同事用某種取自Colloca研究的黑猩猩載體來給一小群健康志愿者注射了一種可能的C型肝炎疫苗,。該黑猩猩病毒載體（與某種罕見的人類腺病毒載體一樣）觸發(fā)了一種對該病毒的特異性的免疫反應(yīng)；它看上去是安全的而且具有良好的耐受性,。在進(jìn)行更為仔細(xì)的觀察時,，該研究團(tuán)隊看到，來自該疫苗的C型肝炎抗原在試驗參與者的體內(nèi)激活了記憶T細(xì)胞,。一旦接觸到某種特別的病原體,，T細(xì)胞可幫助機體識別并擊退未來的入侵者。一則相關(guān)的《觀點欄目》討論了這些發(fā)現(xiàn)及它們對降低持續(xù)性C型肝炎感染率的意義,。（生物谷bioon.com）
doi:10.1126/scitranslmed.3003155
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Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man
Eleanor Barnes1,2,*, Antonella Folgori3,*, Stefania Capone3, Leo Swadling1, Stephen Aston1, Ayako Kurioka1, Joel Meyer1, Rachel Huddart1, Kira Smith1, Rachel Townsend1, Anthony Brown1, et al.
Currently, no vaccine exists for hepatitis C virus (HCV), a major pathogen thought to infect 170 million people globally. Many studies suggest that host T cell responses are critical for spontaneous resolution of disease, and preclinical studies have indicated a requirement for T cells in protection against challenge. We aimed to elicit HCV-specific T cells with the potential for protection using a recombinant adenoviral vector strategy in a phase 1 study of healthy human volunteers. Two adenoviral vectors expressing NS proteins from HCV genotype 1B were constructed based on rare serotypes [human adenovirus 6 (Ad6) and chimpanzee adenovirus 3 (ChAd3)]. Both vectors primed T cell responses against HCV proteins; these T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (genotypes 1A and 3A). HCV-specific T cells consisted of both CD4+ and CD8+ T cell subsets; secreted interleukin-2, interferon-γ, and tumor necrosis factor–α; and could be sustained for at least a year after boosting with the heterologous adenoviral vector. Studies using major histocompatibility complex peptide tetramers revealed long-lived central and effector memory pools that retained polyfunctionality and proliferative capacity. These data indicate that an adenoviral vector strategy can induce sustained T cell responses of a magnitude and quality associated with protective immunity and open the way for studies of prophylactic and therapeutic vaccines for HCV.
