A Single-Dose Q beta VLP Vaccine against S100A9 Protein Reduces Atherosclerosis in a Preclinical Model

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 Q beta 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-1 beta, 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.