a Laboratório de Imunogenética, Departamento de Imunologia , Instituto de Ciências Biomédicas/ICB, Universidade de São Paulo/USP , São Paulo , SP , Brazil.
b Laboratório de Investigação Médica LIM-56, Departamento de Dermatologia , Faculdade de Medicina, Universidade de São Paulo/USP , São Paulo , SP , Brazil.
Hum Vaccin Immunother. 2018;14(8):1995-2002. doi: 10.1080/21645515.2018.1463942. Epub 2018 May 17.
Systems biological analysis has recently revealed how innate immune variants as well as gut microbiota impact the individual response to immunization. HIV-infected (HIV+) patients have a worse response rate after standard vaccinations, possibly due to the immune exhaustion, increased gut permeability and microbial translocation. In the last decade, dendritic cells (DC)-based immunotherapy has been proposed as an alternative approach to control HIV plasma viral load, however clinical trials showed a heterogeneity of immunization response. Hypothesizing that host genetics may importantly affects the outcome of immunotherapy in HIV+ patients, genetic polymorphisms' distribution and gene expression modulation were analyzed in a phase I/II clinical trial of DC-based immunotherapy according to immunization response, and quality of vaccine product (DC). Polymorphisms in genes previously associated with progression of HIV infection to AIDS (i.e.: PARD3B, CCL5) contribute to a better response to immunotherapy in HIV+ individuals, possibly through a systemic effect on host immune system, but also directly on vaccine product. Genes expression profile after immunization correlates with different degrees of immune chronic activation/exhaustion of HIV+ patients (i.e. PD1, IL7RA, EOMES), but also with anti-viral response and DC quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an immunocompetent individual would have a better vaccine response. These findings showed once more that host genetics can affect the response to DC-based immunotherapy in HIV+ individuals, contributing to the heterogeneity of response observed in concluded trials; and it can be used as predictor of immunization success.
系统生物学分析最近揭示了先天免疫变异体以及肠道微生物群如何影响个体对免疫接种的反应。感染 HIV 的（HIV+）患者在接受标准疫苗接种后的反应率较差，这可能是由于免疫衰竭、肠道通透性增加和微生物易位所致。在过去的十年中，基于树突状细胞（DC）的免疫疗法已被提议作为控制 HIV 血浆病毒载量的替代方法，然而临床试验显示免疫接种反应存在异质性。假设宿主遗传学可能对 HIV+患者的免疫疗法结果有重要影响，根据免疫接种反应和疫苗产品（DC）的质量，对基于 DC 的免疫疗法的 I/II 期临床试验中的遗传多态性分布和基因表达调节进行了分析。先前与 HIV 感染进展为艾滋病相关的基因（即：PARD3B、CCL5）的多态性有助于 HIV+个体对免疫疗法有更好的反应，这可能通过对宿主免疫系统的全身性影响，但也直接对疫苗产品产生影响。免疫接种后的基因表达谱与 HIV+患者不同程度的免疫慢性激活/衰竭（即：PD1、IL7RA、EOMES）相关，但也与抗病毒反应和 DC 质量（即：APOBEC3G、IL8、PPIA）相关，这表明免疫功能正常的个体将有更好的疫苗反应。这些发现再次表明，宿主遗传学可以影响 HIV+个体对基于 DC 的免疫疗法的反应，导致结论性试验中观察到的反应异质性；并且可以用作免疫接种成功的预测指标。
