Desain In Silico Vaksin Tolerogenik ApoB100-HLA-DR untuk Mencegah Inisiasi Aterosklerosis

Abstract

Atherosclerosis is a chronic inflammatory disease involving adaptive immune responses against modified apolipoprotein B100 (ApoB100). Presentation of ApoB100 epitopes by MHC class II (HLA-DR) molecules to CD4⁺ T cells contributes to disease initiation and progression. Loss of immune tolerance to ApoB100 provides an opportunity for developing tolerogenic vaccines aimed at immune regulation to prevent atherosclerosis. This study aimed to evaluate the potential of an ApoB100–HLA-DR-based tolerogenic vaccine through an in silico approach. An exploratory in silico analysis was conducted using the human ApoB100 protein. MHC class II epitope prediction was performed, followed by evaluation of antigenicity, toxicity, allergenicity, immunogenicity, physicochemical properties, and molecular docking with HLA-DR molecules. Epitope prediction identified 421 MHC class II epitopes, of which 98 were classified as non-antigenic, non-toxic, and non-allergenic. Immunogenicity analysis selected three epitopes (LRFLKNIIL, FLKNIILPV, and VAVYLESLQ) with potential to induce tolerogenic cytokines IL-10 and IL-2. Structural and physicochemical analyses indicated that the vaccine construct was stable and hydrophilic. Molecular docking showed that cluster 0 exhibited the strongest binding affinity to HLA-DR, indicated by the lowest energy value (−966.6) and the highest number of cluster members, supported by stable non-covalent interactions. In conclusion, the in silico-designed ApoB100–HLA-DR-based tolerogenic vaccine demonstrates potential as a preventive strategy for atherosclerosis, although further experimental validation is required..