Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial.
Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial.
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用编码HIV-1 GAG和NEF的mRNA转染的自体树突状细胞的HIV-1感染者免疫接种：一项随机，安慰剂对照的临床试验的结果。
DOI：
10.1097/qai.0000000000000852
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Kavanagh DG
中科院分区：
文献类型：
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作者：
Gandhi RT;Kwon DS;Macklin EA;Shopis JR;McLean AP;McBrine N;Flynn T;Peter L;Sbrolla A;Kaufmann DE;Porichis F;Walker BD;Bhardwaj N;Barouch DH;Kavanagh DG
根除HIV-1可能需要重新激活潜伏病毒，同时刺激HIV-1特异性免疫反应以清除感染细胞。用转染病毒mRNA的自体树突状细胞（dc）免疫是一种很有前途的激发hiv -1特异性免疫应答的策略。我们进行了一项随机对照临床试验，以评估这种方法在接受抗逆转录病毒治疗的hiv -1感染者中的免疫原性。15名参与者按2:1随机分组，分别在第0、2、6和10周接受HIV-1 Gag-和nef转染dc（疫苗）或模拟转染dc（安慰剂）的皮内免疫接种。所有参与者还接受了锁孔帽贝血青素（KLH）脉冲DCs，以评估是否可以诱导对新抗原的反应。免疫后，疫苗组和安慰剂组对HIV-1 Gag或Nef的干扰素- γ酶联免疫点反应没有差异。接种后CD4细胞对KLH的增殖反应增加2.4倍（P = 0.026）， CD8细胞对KLH的增殖反应增加2.5倍（P = 0.053）。在疫苗接种者中，HIV-1 Gag的CD4增殖反应（与基线相比增加2.5倍，与安慰剂相比增加3.4倍，P = 0.054）和HIV-1 Nef（与基线相比增加2.3倍，与安慰剂相比增加6.3倍，P = 0.009），但这些反应是短暂的。用转染了编码HIV-1 Gag和Nef的mRNA的树突状细胞免疫，没有诱导显著的干扰素- γ酶联免疫斑点反应。对HIV-1抗原和新抗原KLH的增殖反应增加，但这种影响是短暂的。树突状细胞疫苗接种应优化，以引起更强和持久的免疫反应，使该策略成为有效的HIV-1治疗性疫苗。
HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy. Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced. After immunization, there were no differences in interferon-gamma enzyme-linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived. Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme-linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long-lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine.