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DC细胞疫苗诱导的T细胞反应可以控制HIV感染
发布时间: 2013-05-12    人气指数:1276

联合抗逆转录病毒疗法(cART)可以明显改善HIV-1感染者的生存时间和生活质量,然而,该疗法必须无限期坚持用药,否则将会出现病毒反弹和相关的疾病进展。

诱导HIV-1特异性免疫反应来控制HIV-1病毒复制,可能是cART终身治疗的替代手段。

西班牙巴塞罗那大学的Felipe García报告了安全、可耐受的、具有免疫原性的可控制病毒复制的治疗性疫苗,应用自体单核细胞来源的树突状细胞(MD-CDs)冲击治疗自体来源的热灭活HIV病毒。cART治疗的CD4+T细胞计数>450的感染者,随机分组,接受MD-CDs3次免疫冲击治疗或非冲击MD-CDs。疫苗是可行的、安全的、可耐受的,并且达到了宿主/病毒平衡。在干预后的12周和24周,冲击组的血浆病毒滴度降低了一个数量级以上的分别为12/2255% 7/2035%),而对照组只有1/119%)和0/100%)。该降低血浆病毒滴度反应和持续的HIV-1特异性T细胞反应是对应的。

该研究提示:在慢性HIV感染者治疗的早期阶段,在cART治疗后,采用由治疗性DC免疫诱导的HIV-1特异性免疫反应疗法,可以明显降低HIV病毒的血浆病毒滴度。

 

资料来源:Sci Transl Med. 2013;5(166):166ra2


 2013 Jan 2;5(166):166ra2. doi: 10.1126/scitranslmed.3004682.

dendritic cell-based vaccine elicits T cell responses associated with control of HIV-1replication.

Source

Hospital Clinic-IDIBAPS, HIVACAT, University of Barcelona, 08036 Barcelona, Spain.

Abstract

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 immuneresponses 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 viralreplication 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/mm(3) 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 inHIV-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.