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基于树突状细胞的抗HIV免疫疗法:距离成功还有多远?一项系统评价与荟萃分析

Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis.

作者信息

Coelho Antonio Victor Campos, de Moura Ronald Rodrigues, Kamada Anselmo Jiro, da Silva Ronaldo Celerino, Guimarães Rafael Lima, Brandão Lucas André Cavalcanti, de Alencar Luiz Cláudio Arraes, Crovella Sergio

机构信息

Department of Genetics, Federal University of Pernambuco, Avenida da Engenharia, Cidade Universitária, Recife 50740-600, Brazil.

Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Avenida da Engenharia, Cidade Universitária, Recife 50740-600, Brazil.

出版信息

Int J Mol Sci. 2016 Nov 26;17(12):1985. doi: 10.3390/ijms17121985.

Abstract

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.

摘要

科学界在制定治愈HIV-1的策略方面仍面临挑战。其中一种正在探索的策略是开发基于树突状细胞(DCs)的免疫治疗疫苗,用病毒脉冲处理这些细胞,旨在增强针对HIV-1的特异性免疫反应。我们旨在回顾基于DCs的治疗性疫苗报告,并严格评估证据,以获取改进这些策略的见解。我们对临床试验报告进行了系统回顾,随后进行了荟萃分析和荟萃回归。选择了12项研究进行荟萃分析。实验性疫苗效率较低,总体成功率约为38%(95%置信区间=26.7%-51.3%)。尽管多变量分析未显示抗原选择、DC培养方法和剂量中的任何一项对总体成功率有影响,但方案因这些因素而异。基于DCs的疫苗至少引发了一些免疫原性,有时与血浆病毒载量的短暂控制有关。这些方案纳入了初治和接受过抗逆转录病毒治疗(ART)的个体,并使用了不同的标准来评估疫苗疗效。尽管疫苗未能达到预期效果,但它们证明了可以增强针对HIV-1的免疫反应这一概念。方案标准化以及使用辅助方法,如激活潜伏的HIV-1储存库和患者基因组学,对于优化未来的HIV-1治愈策略至关重要。

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