A Single‐Dose Qβ VLP Vaccine against S100A9 Protein Reduces Atherosclerosis in a Preclinical Model
Oscar A. Ortega‐Rivera, Matthew D. Shin, Miguel A. Moreno‐Gonzalez, Jonathan K. Pokorski, Nicole F. Steinmetz
Abstract
Abstract 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.