Knuschke Torben, Bayer Wibke, Rotan Olga, Sokolova Viktoriya, Wadwa Munisch, Kirschning Carsten J, Hansen Wiebke, Dittmer Ulf, Epple Matthias, Buer Jan, Westendorf Astrid M
Institute of Medical Microbiology, University Hospital Essen, University of Duisburg- Essen, Essen, Germany.
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Nanomedicine. 2014 Nov;10(8):1787-98. doi: 10.1016/j.nano.2014.06.014. Epub 2014 Jul 9.
Retroviral infections e.g. HIV still represent a unique burden in the field of vaccine research. A common challenge in vaccine design is to find formulations that create appropriate immune responses to protect against and/or control the given pathogen. Nanoparticles have been considered to be ideal vaccination vehicles that mimic invading pathogens. In this study, we present biodegradable calcium phosphate (CaP) nanoparticles, functionalized with CpG and retroviral T cell epitopes of Friend virus (FV) as excellent vaccine delivery system. CaP nanoparticles strongly increased antigen delivery to antigen-presenting cells to elicit a highly efficient T cell-mediated immune response against retroviral FV infection. Moreover, single-shot immunization of chronically FV-infected mice with functionalized CaP nanoparticles efficiently reactivated effector T cells which led to a significant decrease in viral loads. Thus, our findings clearly indicate that a nanoparticle-based peptide immunization is a promising approach to improve antiretroviral vaccination.
In this study, biodegradable calcium phosphate nanoparticles were used as a vaccine delivery system after functionalization with CpG and Friend virus-derived T-cell epitopes. This vaccination strategy resulted in increased T-cell mediated immune response even in chronically infected mice, providing a promising approach to the development of clinically useful antiretroviral vaccination strategies.
逆转录病毒感染,例如HIV,在疫苗研究领域仍然是一个独特的负担。疫苗设计中的一个常见挑战是找到能够产生适当免疫反应以预防和/或控制特定病原体的制剂。纳米颗粒被认为是模仿入侵病原体的理想疫苗载体。在本研究中,我们展示了用CpG和Friend病毒(FV)的逆转录病毒T细胞表位功能化的可生物降解磷酸钙(CaP)纳米颗粒,作为出色的疫苗递送系统。CaP纳米颗粒极大地增加了向抗原呈递细胞的抗原递送,以引发针对逆转录病毒FV感染的高效T细胞介导的免疫反应。此外,用功能化的CaP纳米颗粒对慢性FV感染的小鼠进行单次免疫可有效重新激活效应T细胞,这导致病毒载量显著降低。因此,我们的研究结果清楚地表明,基于纳米颗粒的肽免疫是改善抗逆转录病毒疫苗接种的一种有前景的方法。
在本研究中,可生物降解的磷酸钙纳米颗粒在被CpG和Friend病毒衍生的T细胞表位功能化后用作疫苗递送系统。这种疫苗接种策略即使在慢性感染的小鼠中也能增强T细胞介导的免疫反应,为开发临床上有用的抗逆转录病毒疫苗接种策略提供了一种有前景的方法。