The standard therapy for cardiovascular disease (CVD) is the administration of statins to reduce plasma cholesterol levels, but this requires lifelong treatment. We developed a CVD vaccine candidate that targets the pro-inflammatory mediator calprotectin by eliciting antibodies against the S100A9 protein. The vaccine, based on bacteriophage Qβ virus-like particles (VLPs) displaying S100A9 peptide epitopes, was formulated as a slow-release PLGA:VLP implant by hot-melt extrusion. The single-dose implant elicited 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 reduced serum levels of calprotectin, IL-1β, IL-6 and MCP-1, resulting in less severe aortic lesions. This novel implant was 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.
Keyphrases
- cardiovascular disease
- high fat diet
- soft tissue
- insulin resistance
- adipose tissue
- type diabetes
- drug delivery
- aortic valve
- high frequency
- cognitive decline
- cardiovascular events
- left ventricular
- metabolic syndrome
- stem cells
- bone marrow
- binding protein
- early onset
- combination therapy
- atrial fibrillation
- rheumatoid arthritis
- small molecule
- mesenchymal stem cells
- mild cognitive impairment
- high fat diet induced
- coronary artery disease