biostudies-literatureMalensek SThe Slovenian Research and Innovation AgencyHorizon Europe101535https://www.ebi.ac.uk/biostudies/studies/S-EPMC12356014biostudies-literatureUnknown33(3)Cardiovascular diseases, especially atherosclerosis, are the main cause of death in the whole world. The risk can be reduced by lowering the serum low-density lipoprotein cholesterol by targeting proprotein convertase 9 (PCSK9) through genome editing or neutralization by monoclonal antibodies. Vaccination against PCSK9 represents an alternative with potentially long-lasting efficacy, but must overcome the challenge of immunogenicity against the endogenous protein, which can also elicit lower antibody response due to B cell tolerance. In contrast to the previously reported weakly immunogenic PCSK9 peptides, we have developed a designed chimeric PCSK9 that maintains the surface epitopes and elicits a B cell immune response with PCSK9-specific antibodies, comparable to human-based vaccines, bMolecular therapy. Methods & clinical developmentEngineering chimeric PCSK9 for a vaccine against atherosclerosis.PMC12356014101059842P4-0176J3-4526Lainscek DEsih HBlinc AUrbanc AGMalensek SOrehek SFink TJerala RfalseEngineering chimeric PCSK9 for a vaccine against atherosclerosis.Cardiovascular diseases, especially atherosclerosis, are the main cause of death in the whole world. The risk can be reduced by lowering the serum low-density lipoprotein cholesterol by targeting proprotein convertase 9 (PCSK9) through genome editing or neutralization by monoclonal antibodies. Vaccination against PCSK9 represents an alternative with potentially long-lasting efficacy, but must overcome the challenge of immunogenicity against the endogenous protein, which can also elicit lower antibody response due to B cell tolerance. In contrast to the previously reported weakly immunogenic PCSK9 peptides, we have developed a designed chimeric PCSK9 that maintains the surface epitopes and elicits a B cell immune response with PCSK9-specific antibodies, comparable to human-based vaccines, b2025-01-01T00:00:00Z2025 Sep2026-07-15T12:40:09.497Z2026-07-04T03:14:38.915ZS-EPMC123560144082185410.1016/j.omtm.2025.101535