New HIV-vaccine tested on people. (Credit： Image courtesy of Institute of Tropical Medicine Antwerp)
近日，來(lái)自安特衛(wèi)普大學(xué)和安特衛(wèi)普醫(yī)院的研究人員用一種治療HIV的疫苗對(duì)第一批志愿者進(jìn)行測(cè)試,，研究者從志愿者體內(nèi)取出白血細(xì)胞，注射入疫苗,，然后輸送回志愿者體內(nèi)，一段時(shí)間后,，志愿者體內(nèi)的免疫反應(yīng)表現(xiàn)良好,，在攻擊和壓制病毒復(fù)制上表現(xiàn)比原來(lái)好，這樣研究結(jié)果已于近日刊登于國(guó)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(shí)上,，我們可以用雞尾酒內(nèi)服藥混合物來(lái)有效的控制HIV的復(fù)制感染,，但是當(dāng)被艾滋病病毒感染者患者停止了積極的治療，HIV病毒便會(huì)繼續(xù)復(fù)制,，繼續(xù)危害人體,。科學(xué)界都知道,，我們?nèi)梭w的堅(jiān)固防線(xiàn)CD8+細(xì)胞的量并不是很足夠,，人類(lèi)的樹(shù)突狀細(xì)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(xì)胞,，安特衛(wèi)普大學(xué)的病毒學(xué)家和HIV血液病專(zhuān)家在治療HIV感染的課題上合作多年,，研究者在實(shí)驗(yàn)室中將樹(shù)突細(xì)胞（以信使RNA疫苗的形式）輸入進(jìn)感染者體內(nèi),，從而建立對(duì)HIV蛋白的相關(guān)指令,。樹(shù)突細(xì)胞將嚴(yán)密監(jiān)控指令，將HIV表面的重要信息進(jìn)行展現(xiàn),，后期的研究中,，研究者們證實(shí)了,，被輸入進(jìn)感染者體內(nèi)的樹(shù)突細(xì)胞的確可以激活體內(nèi)免疫細(xì)胞對(duì)HIV病毒的攻擊。
在后期,，6位長(zhǎng)期用雞尾酒內(nèi)服藥混合物長(zhǎng)期治療的感染者將作為志愿者進(jìn)行此項(xiàng)研究,，研究者從志愿者體內(nèi)濾出樹(shù)突細(xì)胞，然后在細(xì)胞培養(yǎng)室中進(jìn)行培養(yǎng),，給予其針對(duì)HIV病毒的遺傳指令,，隨后將細(xì)胞凍結(jié)。隨后研究者每隔四周給志愿者體內(nèi)輸入一次被賦予遺傳指令的樹(shù)突細(xì)胞,，共進(jìn)行了四次,，這種接種對(duì)志愿者沒(méi)有任何副作用；結(jié)果表明,，志愿者體內(nèi)的CD8+細(xì)胞可以更好的識(shí)別HIV病毒,，并對(duì)其進(jìn)行攻擊，研究者的這項(xiàng)研究最重要的一點(diǎn)就是,，他們利用疫苗激活免疫細(xì)胞,，免疫細(xì)胞進(jìn)而對(duì)病毒進(jìn)行有效的壓制，并且抵御HIV的感染,。但是HIV病毒比較會(huì)進(jìn)行自我偽裝,，它們會(huì)很快地改變外表的蛋白，讓一部分病毒逃過(guò)攻擊,，從而繼續(xù)進(jìn)行復(fù)制感染,。
作者表示，目前這種方法不可能完全治愈AIDS,，但是結(jié)果很令人高興,，通過(guò)志愿者樹(shù)突細(xì)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.
