Sci Transl Med：新型治疗性疫苗能暂时抑制HIV生长

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一个西班牙研究小组的研究人员称，他们开发出了一种治疗性疫苗，能够暂时地抑制感染患者体内的HIV生长。

这种疫苗是利用接触热灭活HIV的免疫细胞研制而成，研究人员针对36名HIV携带者进行了测试，获得了这类治疗最好的记录结果。

研究小组成员、巴塞罗那大学医院Felipe Garcia说：“我们所做的就是给予免疫系统指令，使其学会自然情况下无法做到的事情——破坏HIV病毒。”

研究人员说，这一治疗性疫苗并非用来预防疾病，而是用于治疗已存在的艾滋病。其非常安全，可使一些患者体内检测到的HIV病毒数量显着降低。相关研究发布在《科学—转化医学》（Science Translational Medicine）杂志上。

经过12周的临床试验，在22名接种疫苗的患者中，有12人HIV病毒载量降低了90%以上。11名接受对照注射的患者中，只有1人获得了相似的结果。

24周后，疫苗的效力开始下降，在剩余的20名疫苗接种患者中，有7人病毒载量下降了90%。对照组10名患者无一人病毒量下降。

疫苗在一年后丧失效力，此时患者必须恢复他们常规的抗逆转录病毒药物组合治疗。

研究人员说这些结果与采用单一抗逆转录病毒药物阻断HIV生长所获得的结果相似。

“这是在科学文献中提供的最坚实的证明，表明治疗性疫苗是有可能的，”研究人员在一份声明中说。

这种疫苗使得患者可以暂时摆脱每日服用多种药物，坚持每日服药对于患者存在困难，且长期而言会造成毒副作用，并需付出昂贵的经济代价。

“这一调查研究为开展其他的研究，最终达到功能性治愈的目的，无需抗逆转录病毒治疗长期或终身控制HIV复制，开辟了新途径，”研究人员说。

“虽然我们还没有获得功能性治愈，今天发布的研究结果为获得一种最佳的治疗疫苗，或是涵盖治疗疫苗的一种组合策略提供了可能性，并且可能有助于实现这一目标，”他们说。

研究小组表示他们投入了7年的时间才走到这一步，现在他们正在致力于改良这一疫苗，争取在未来的三四年间使之与其他的治疗性疫苗相结合。

http://www.bioon.com/biology/Immunology/540035.shtml

A Dendritic Cell–Based Vaccine Elicits T Cell Responses Associated with Control of HIV-1 Replication

Felipe García1,*,†, Nuria Climent1,*, Alberto C. Guardo1, Cristina Gil1, Agathe León1, Brigitte Autran2,Jeffrey D. Lifson3, Javier Martínez-Picado4,5, Judit Dalmau4, Bonaventura Clotet4, Josep M. Gatell1,Montserrat Plana1,*, Teresa Gallart1,*, For the DCV2/MANON07-ORVACS Study Group

Combination antiretroviral therapy (cART) greatly improves survival and quality of life of HIV-1–infected patients; however, cART must be continued indefinitely to prevent viral rebound and associated disease progression. Inducing HIV-1–specific immune responses with a therapeutic immunization has been proposed to control viral replication after discontinuation of cART as an alternative to “cART for life.” We report safety, tolerability, and immunogenicity results associated with a control of viral replication for a therapeutic vaccine using autologous monocyte-derived dendritic cells (MD-DCs) pulsed with autologous heat-inactivated whole HIV. Patients on cART with CD4+ >450 cells/mm3 were randomized to receive three immunizations with MD-DCs or with nonpulsed MD-DCs. Vaccination was feasible, safe, and well tolerated and shifted the virus/host balance. At weeks 12 and 24 after cART interruption, a decrease of plasma viral load setpoint ≥1 log was observed in 12 of 22 (55%) versus 1 of 11 (9%) and in 7 of 20 (35%) versus 0 of 10 (0%) patients in the DC–HIV-1 and DC-control groups, respectively. This significant decrease in plasma viral load observed in immunized recipients was associated with a consistent increase in HIV-1–specific T cell responses. These data suggest that HIV-1–specific immune responses elicited by therapeutic DC vaccines could significantly change plasma viral load setpoint after cART interruption in chronic HIV-1–infected patients treated in early stages. This proof of concept supports further investigation of new candidates and/or new optimized strategies of vaccination with the final objective of obtaining a functional cure as an alternative to cART for life.

http://stm.sciencemag.org/conten ... 0-bd37-eaa321df2ae4