Klein M R, Veenstra J, Holwerda A M, Roos M T, Gow I, Patou G, Coutinho R A, De Wolf F, Miedema F
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
AIDS Res Hum Retroviruses. 1997 Mar 20;13(5):393-9. doi: 10.1089/aid.1997.13.393.
Gag-specific immune responses and changes in HIV-1 RNA levels were evaluated in eight HIV-1-infected persons, in order to assess the immunotherapeutic potential HIV-1 p17/p24: Ty virus-like particles (p24-VLP). All treated subjects showed transient and dose-dependent proliferative responses to the Ty-VLP carrier (stimulation index [SI], 2.0-119.5). Three of four individuals who received either 500 or 1,000 micrograms of p24-VLP also showed proliferative responses to p17 or p24 (SI, 2.0-15.7). In 2 subjects who were treated with either 500 or 1,000 micrograms of p24-VLP, enhanced Gag-specific CTL precursor (CTLp) frequencies were observed after immunization (10- to 14-fold). Both subjects had low baseline Gag-specific CTL activity (< 25 cTLp/10(6) PBMCs). In the other participants studied no significant boosting of preexisting Gag-specific CTL responses was observed. Short-term elevation of HIV-1 RNA levels at weeks 2 and 4 was observed in two subjects treated with the highest dose of p24-VLP. However, HIV-1 RNA levels at week 24 did not significantly differ from those found in the placebo group. In conclusion, p24-VLP induced marginal Gag-specific immune responses in limited numbers of HIV-1-seropositive individuals, with some showing transient elevation of HIV-1 viral load. Further studies are needed to establish potential clinical effects of these observations.
在八名HIV-1感染者中评估了针对Gag的免疫反应以及HIV-1 RNA水平的变化，以评估HIV-1 p17/p24：Ty病毒样颗粒（p24-VLP）的免疫治疗潜力。所有接受治疗的受试者对Ty-VLP载体均表现出短暂且剂量依赖性的增殖反应（刺激指数[SI]，2.0-119.5）。在接受500或1000微克p24-VLP治疗的四名个体中，有三名也对p17或p24表现出增殖反应（SI，2.0-15.7）。在两名接受500或1000微克p24-VLP治疗的受试者中，免疫后观察到Gag特异性CTL前体（CTLp）频率增加（10至14倍）。这两名受试者的基线Gag特异性CTL活性均较低（<25 cTLp/10(6) PBMCs）。在其他研究参与者中，未观察到对既往存在的Gag特异性CTL反应有明显增强。在接受最高剂量p24-VLP治疗的两名受试者中，在第2周和第4周观察到HIV-1 RNA水平短期升高。然而，第24周时的HIV-1 RNA水平与安慰剂组无显著差异。总之，p24-VLP在有限数量的HIV-1血清阳性个体中诱导了微弱的Gag特异性免疫反应，部分个体出现HIV-1病毒载量短暂升高。需要进一步研究来确定这些观察结果的潜在临床影响。
