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A Single-Dose Qβ VLP Vaccine against S100A9 Protein Reduces Atherosclerosis in a Preclinical Model
Advanced Therapeutics ( IF 4.6 ) Pub Date : 2022-07-07 , DOI: 10.1002/adtp.202200092
Oscar A Ortega-Rivera 1, 2 , Matthew D Shin 1, 2 , Miguel A Moreno-Gonzalez 1, 2 , Jonathan K Pokorski 1, 2, 3 , Nicole F Steinmetz 1, 2, 3, 4, 5, 6
Affiliation  

The standard therapy for cardiovascular disease (CVD) is the administration of statins to reduce plasma cholesterol levels, but this requires lifelong treatment. A CVD vaccine candidate that targets the pro-inflammatory mediator calprotectin by eliciting antibodies against the S100A9 protein is developed. The vaccine, based on bacteriophage Qβ virus-like particles (VLPs) displaying S100A9 peptide epitopes, is formulated as a slow-release PLGA:VLP implant by hot–melt extrusion. The single-dose implant elicits S100A9-specific antibody titers comparable to a three-dose injection schedule with soluble VLPs. In an animal model of CVD (ApoE−/− mice fed on a high-fat diet), the implant reduces serum levels of calprotectin, IL-1β, IL-6, and MCP-1, resulting in less severe aortic lesions. This novel implant is therefore able to attenuate atherosclerosis over a sustained period and offers a novel and promising strategy to replace the repetitive administration of statins for the treatment of CVD.

中文翻译:

针对 S100A9 蛋白的单剂量 Qβ VLP 疫苗可减少临床前模型中的动脉粥样硬化

心血管疾病(CVD)的标准疗法是使用他汀类药物来降低血浆胆固醇水平,但这需要终身治疗。开发了一种 CVD 候选疫苗,通过引发针对 S100A9 蛋白的抗体来靶向促炎介质钙卫蛋白。该疫苗基于显示 S100A9 肽表位的噬菌体 Qβ 病毒样颗粒 (VLP),通过热熔挤出配制为缓释 PLGA:VLP 植入物。单剂量植入物引发的 S100A9 特异性抗体滴度与可溶性 VLP 的三剂量注射方案相当。在 CVD 动物模型(高脂饮食喂养的 ApoE −/− 小鼠)中,植入物降低了钙卫蛋白、IL-1β、IL-6 和 MCP-1 的血清水平,从而减轻了主动脉病变的严重程度因此,这种新型植入物能够在持续一段时间内减轻动脉粥样硬化,并提供一种新颖且有前景的策略来取代重复施用他汀类药物来治疗 CVD。
更新日期:2022-07-07
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