Bekele Yonas, Graham Rebecka Lantto, Soeria-Atmadja Sandra, Nasi Aikaterini, Zazzi Maurizio, Vicenti Ilaria, Naver Lars, Nilsson Anna, Chiodi Francesca
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
Front Immunol. 2018 Jan 10;8:1966. doi: 10.3389/fimmu.2017.01966. eCollection 2017.
During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory) and CD8+ (central memory) T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced frequency of activated CD4+ cells and an increase in central memory CD8+ T cells were associated with this finding. Further studies should assess whether vaccination is a possible tool to reduce HIV-1 reservoirs.
在抗逆转录病毒疗法(ART)期间,HIV-1持续存在于细胞储存库中,主要以CD4+记忆T细胞为代表。目前正在采取多种方法,通过消除(或减少)这些储存库来开发治愈HIV-1感染的方法。到目前为止,很少有研究评估在病毒学得到控制的HIV-1感染儿童中通过接种疫苗来缩小HIV-1储存库规模的可能性。我们最近对22名HIV-1感染儿童进行了一项联合甲型肝炎病毒(HAV)和乙型肝炎病毒(HBV)疫苗的接种研究。我们评估了接种疫苗前后作为血细胞中HIV-1总DNA拷贝数衡量的病毒储存库规模。此外,我们通过免疫染色研究了接种疫苗是否调节了CD4+和CD8+ T细胞的频率以及这些细胞上的免疫激活和增殖参数。在最后一剂疫苗接种后1个月,我们发现22名儿童中有20名对HBV产生了血清学反应;大多数儿童在基线时就有抗HAV抗体。与基线相比,接种疫苗后1个月血液中HIV-1 DNA拷贝数有所减少,尽管这种减少没有统计学意义。在12名儿童中发现接种疫苗后血液中HIV-1 DNA拷贝数显著减少。接种疫苗后,CD4+(初始、效应记忆)和CD8+(中枢记忆)T细胞亚群的频率发生了变化,并且还注意到这些细胞的激活和增殖模式有所减少。多变量线性回归分析显示,接种疫苗前CD8+效应记忆T细胞的频率强烈预测了22名HIV-1感染儿童接种疫苗后血液中HIV-1 DNA拷贝数的减少。这项研究的结果表明,接种疫苗对接受ART治疗 的HIV-1感染儿童缩小病毒储存库规模有有益作用。活化CD4+细胞频率降低和中枢记忆CD8+ T细胞增加与这一发现相关。进一步的研究应评估接种疫苗是否是减少HIV-1储存库的一种可能工具。