Computational Design of a Multi-Epitope Peptide Vaccine Against the Opportunistic Fungus Aspergillus fumigatus in Lung Cancer Patients

Opportunistic Aspergillus fumigatus infections pose a serious threat to immunocompromised individuals, particularly lung cancer patients undergoing chemotherapy or immunosuppressive therapy. This study reports the in-silico design of a multi-epitope peptide vaccine targeting two extracellular cell-wall enzymes, Crh-like protein 5 and 1,3-β-glucanosyltransferase, identified through proteome screening and subcellular localization analysis. Linear and conformational B-cell, CTL, and HTL epitopes were predicted and filtered for antigenicity, non-allergenicity, and non-toxicity, yielding six rationally assembled constructs with suitable adjuvants and linkers. Molecular docking with TLR5 and HLA-DR1, followed by structural validation and physicochemical profiling, identified Construct-3 as the most stable and antigenic (VaxiJen = 1.16, non-allergenic, non-toxic). Molecular dynamics simulations (100 ns) confirmed stable receptor binding with minimal conformational fluctuations, and population-coverage analysis predicted ~ 59% global HLA representation. These results highlight Construct-3 as a structurally validated and immunogenically robust vaccine candidate warranting experimental evaluation against A. fumigatus in lung cancer patients.