New HIV-vaccine tested on people. (Credit： Image courtesy of Institute of Tropical Medicine Antwerp)
近日，来自安特卫普大学和安特卫普医院的研究人员用一种治疗HIV的疫苗对第一批志愿者进行测试，研究者从志愿者体内取出白血细胞，注射入疫苗，然后输送回志愿者体内，一段时间后，志愿者体内的免疫反应表现良好，在攻击和压制病毒复制上表现比原来好，这样研究结果已于近日刊登于国际杂志AIDS上，但研究者表示，目前还不能完全治愈这种疾病。
事实上，我们可以用鸡尾酒内服药混合物来有效的控制HIV的复制感染，但是当被艾滋病病毒感染者患者停止了积极的治疗，HIV病毒便会继续复制，继续危害人体。科学界都知道，我们人体的坚固防线CD8+细胞的量并不是很足够，人类的树突状细胞并不能很好地获取HIV病毒的有效信息，并不能将完整的信息反馈给CD8+细胞，安特卫普大学的病毒学家和HIV血液病专家在治疗HIV感染的课题上合作多年，研究者在实验室中将树突细胞（以信使RNA疫苗的形式）输入进感染者体内，从而建立对HIV蛋白的相关指令。树突细胞将严密监控指令，将HIV表面的重要信息进行展现，后期的研究中，研究者们证实了，被输入进感染者体内的树突细胞的确可以激活体内免疫细胞对HIV病毒的攻击。
在后期，6位长期用鸡尾酒内服药混合物长期治疗的感染者将作为志愿者进行此项研究，研究者从志愿者体内滤出树突细胞，然后在细胞培养室中进行培养，给予其针对HIV病毒的遗传指令，随后将细胞冻结。随后研究者每隔四周给志愿者体内输入一次被赋予遗传指令的树突细胞，共进行了四次，这种接种对志愿者没有任何副作用；结果表明，志愿者体内的CD8+细胞可以更好的识别HIV病毒，并对其进行攻击，研究者的这项研究最重要的一点就是，他们利用疫苗激活免疫细胞，免疫细胞进而对病毒进行有效的压制，并且抵御HIV的感染。但是HIV病毒比较会进行自我伪装，它们会很快地改变外表的蛋白，让一部分病毒逃过攻击，从而继续进行复制感染。
作者表示，目前这种方法不可能完全治愈AIDS，但是结果很令人高兴，通过志愿者树突细胞制造的疫苗，很安全，而且也是一种很有效的抵御HIV病毒的方法。（生物谷： T.Shen编译）
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.
