Proteome-Based Antigen Screening and Multi-Epitope Design Against Cutibacterium acnes: An In Silico Study

Inflammation plays a pivotal role in the pathogenesis of acne vulgaris, with Cutibacterium acnes recognised as a key etiological agent. The global increase in acne prevalence, coupled with the rising incidence of antibiotic-resistant strains, underscores the necessity for alternative therapeutic strategies. Vaccination has emerged as a promising approach, with various candidates targeting live-attenuated strains and specific virulence factors. Nevertheless, the expanding availability of C. acnes genomic data presents an opportunity to identify previously uncharacterized antigens that hold potential as novel targets for the development of next-generation acne vaccines. Therefore, this study aimed to identify core proteins among C. acnes genomes and evaluate their immunogenicity as potential multi-epitope peptide constructs. In addition, IA1-specific proteins of C. acnes were examined to develop the peptide constructs targeting acne-associated isolates. Pan-core analysis of 609 genomes identified 972 core genes. These genes were subsequently analysed for epitope prediction and antigenicity, and the highly antigenic epitopes were selected and combined for further analysis. Multi-epitope peptides were constructed based on predicted MHC-I, MHC-II, and linear B-cell epitopes, yielding four promising candidates derived from C. acnes core proteins and IA1-specific proteins. Molecular docking analysis indicated that both groups showed binding affinity for TLR2 and TLR4 receptors, suggesting possible molecular compatibility with these receptors. Furthermore, in silico immune simulations indicated that both types of multi-epitope peptides were associated with simulated humoral and cellular immune response profiles, although these responses require experimental validation. This computational workflow may help narrow the selection of potential acne vaccine candidates and prioritise multi-epitope peptide constructs for subsequent vaccine design steps and experimental validation.