Dissecting the influence of HIV infection and treatment with antiretroviral therapy on Human Papillomavirus infection, disease and immunity - Identifying possible targets for therapeutic intervention

剖析 HIV 感染和抗逆转录病毒治疗对人乳头瘤病毒感染、疾病和免疫的影响 - 确定治疗干预的可能目标

• 批准号: 214427304
• 负责人: Dr. Christof Geldmacher
• 金额: --
• 依托单位: Abteilung für Infektions- und Tropenmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/214427304?language=en
• 关键词: Dissecting; influence; HIV; infection; treatment

The increase in Human Papilloma Virus (HPV) associated cervical cancer in HIV+ women implies that defects in the HPV-specific CD4 T cell response play an important role in pathogenesis. It can thus be hypothesized that depletion and dysfunction of HPV-specific T cell and antibody responses after HIV infection and even after initiation of highly active antiretroviral therapy (HAART) contribute to frequent HPV reinfection, increased diversity and persistence of High Risk (HR) HPV types finally leading to malignant cell transformation. We postulate that a therapeutic HPV vaccine consisting of selected antigenic targets can specifically prime and reconstitute HPV-specific adaptive immunity to prevent HPV disease progression in HIV+ individuals on HAART. The proposed study aims to elucidate the complicated interplay between HIV, the immune system and HPV induced carcinogenesis in the era of HAART, HPV antigenic regions frequently recognized by the HPV-specific T cell response will be mapped in immunocompetent women and will provide the basis for rationale design of a vaccine tailored for the HR HPV types most frequently occurring in HIV+ subjects. During a later stage, a side study, which will seek additional ethical approval, is planned to explore the safety and immunogenicity of a TFDA* approved subunit vaccine (Gardasil™) or a HPV16 peptide-based vaccine (ISA Pharmaceuticals) in healthy HIV+ women on HAART

HIV阳性妇女中人乳头瘤病毒（HPV）相关宫颈癌的增加意味着HPV特异性CD4 T细胞应答的缺陷在发病机制中起重要作用。因此，可以假设，HIV感染后，甚至在启动高效抗逆转录病毒治疗（HAART）后，HPV特异性T细胞和抗体应答的耗竭和功能障碍导致频繁的HPV再感染，高风险（HR）HPV类型的多样性和持久性增加，最终导致恶性细胞转化。我们假设，由选定的抗原靶点组成的治疗性HPV疫苗可以特异性地引发和重建HPV特异性适应性免疫，以预防HAART HIV+个体的HPV疾病进展。拟议的研究旨在阐明HAART时代HIV、免疫系统和HPV诱导的致癌作用之间的复杂相互作用，HPV特异性T细胞应答经常识别的HPV抗原区域将在免疫功能正常的女性中定位，并将为针对HIV+受试者中最常见的HR HPV类型定制的疫苗的基本原理设计提供基础。在后期阶段，计划进行一项将寻求额外伦理批准的副研究，以探索TFDA* 批准的亚单位疫苗（Gardasil™）或基于HPV 16肽的疫苗（伊萨Pharmaceuticals）在接受HAART的健康HIV+女性中的安全性和免疫原性