New HIV-vaccine tested on people. (Credit: Image courtesy of Institute of Tropical Medicine Antwerp)
近日,,來自安特衛(wèi)普大學和安特衛(wèi)普醫(yī)院的研究人員用一種治療HIV的疫苗對第一批志愿者進行測試,,研究者從志愿者體內取出白血細胞,注射入疫苗,,然后輸送回志愿者體內,,一段時間后,志愿者體內的免疫反應表現(xiàn)良好,,在攻擊和壓制病毒復制上表現(xiàn)比原來好,,這樣研究結果已于近日刊登于國際雜志AIDS上,但研究者表示,,目前還不能完全治愈這種疾病,。
事實上,我們可以用雞尾酒內服藥混合物來有效的控制HIV的復制感染,,但是當被艾滋病病毒感染者患者停止了積極的治療,,HIV病毒便會繼續(xù)復制,,繼續(xù)危害人體??茖W界都知道,,我們人體的堅固防線CD8+細胞的量并不是很足夠,人類的樹突狀細胞并不能很好地獲取HIV病毒的有效信息,,并不能將完整的信息反饋給CD8+細胞,,安特衛(wèi)普大學的病毒學家和HIV血液病專家在治療HIV感染的課題上合作多年,研究者在實驗室中將樹突細胞(以信使RNA疫苗的形式)輸入進感染者體內,,從而建立對HIV蛋白的相關指令,。樹突細胞將嚴密監(jiān)控指令,將HIV表面的重要信息進行展現(xiàn),,后期的研究中,,研究者們證實了,被輸入進感染者體內的樹突細胞的確可以激活體內免疫細胞對HIV病毒的攻擊,。
在后期,,6位長期用雞尾酒內服藥混合物長期治療的感染者將作為志愿者進行此項研究,研究者從志愿者體內濾出樹突細胞,,然后在細胞培養(yǎng)室中進行培養(yǎng),,給予其針對HIV病毒的遺傳指令,隨后將細胞凍結,。隨后研究者每隔四周給志愿者體內輸入一次被賦予遺傳指令的樹突細胞,,共進行了四次,這種接種對志愿者沒有任何副作用,;結果表明,,志愿者體內的CD8+細胞可以更好的識別HIV病毒,并對其進行攻擊,,研究者的這項研究最重要的一點就是,,他們利用疫苗激活免疫細胞,免疫細胞進而對病毒進行有效的壓制,,并且抵御HIV的感染,。但是HIV病毒比較會進行自我偽裝,它們會很快地改變外表的蛋白,,讓一部分病毒逃過攻擊,,從而繼續(xù)進行復制感染。
作者表示,,目前這種方法不可能完全治愈AIDS,,但是結果很令人高興,通過志愿者樹突細胞制造的疫苗,,很安全,,而且也是一種很有效的抵御HIV病毒的方法,。(生物谷: T.Shen編譯)
doi:10.1097/QAD.0b013e32834f33e8
PMC:
PMID:
mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients
Van Gulck, Ellena,*; Vlieghe, Erikab,*; Vekemans, Marcb,*; Van Tendeloo, Viggo F.I.c,d,*; Van De Velde, Annc,d; Smits, Evelienc,d; Anguille, Sébastienc,d; Cools, Nathaliec,d; Goossens, Hermanc; Mertens, Liesbetb; De Haes, Winnia; Wong, Johnssone; Florence, Ericb,*; Vanham, Guidoa,f,g,*; Berneman, Zwi N.c,d,*
Background: In an effort to raise protective antiviral immunity, dendritic cell immunotherapy was evaluated in six adults infected with human immunodeficiency virus (HIV)-1 and stable under highly active antiretroviral therapy (HAART). Design and methods: Autologous monocyte-derived dendritic cells electroporated with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered, whereas patients remained on HAART. Feasibility, safety, immunogenicity and antiviral responses were investigated. Results: Dendritic cell vaccine preparation and administration were successful in all patients and only mild adverse events were seen. There was a significant increase post-dendritic cell as compared to pre-dendritic cell vaccination in magnitude and breadth of HIV-1-specific interferon (IFN)-γ response, in particular to Gag, and in T-cell proliferation. Breadth of IFN-γ response and T-cell proliferation were both correlated with CD4+ and CD8+ polyfunctional T-cell responses. Importantly, dendritic cell vaccination induced or increased the capacity of autologous CD8+ T cells to inhibit superinfection of CD4+ T cells with the vaccine-related IIIB virus and some but not all other HIV-1 strains tested. This HIV-1-inhibitory activity, indicative of improved antiviral response, was correlated with magnitude and breadth of Gag-specific IFN-γ response. Conclusions: Therapeutic immunization with dendritic cells was safe and successful in raising antiviral cellular immune responses, including effector CD8+ T cells with virus inhibitory activity. The stimulation of those potent immunological and antiviral effects, which have been associated with control of HIV-1, underscores the potential of dendritic cell vaccination in the treatment of HIV-1. The incomplete nature of the response in some patients helped to identify potential targets for future improvement, that is increasing antigenic spectrum and enhancing T-cell response.