Invasive aspergillosis (IA), a life-threatening fungal infection predominantly caused by Aspergillus fumigatus, has emerged as a major global health threat, particularly in immunocompromised individuals. The rising resistance of A. fumigatus to existing antifungal therapies, coupled with the lack of an approved vaccine, highlights the urgent need for novel preventive strategies. This study aimed to design multi-epitope vaccines against IA using immunoinformatics approaches. Two highly conserved 1,3-beta-glucanosyltransferase proteins, essential for fungal cell wall remodeling, were identified as potential antigen targets via subtractive proteomics. From these, 13 optimal T-cell and 10 ideal B-cell epitopes were selected to develop two vaccine constructs, designated WLaf1 and WLaf2. Both vaccine constructs exhibited favorable physicochemical stability, antigenicity, and non-allergenicity. Molecular docking and molecular dynamics (MD) analyses suggested stable interactions between the vaccine constructs and innate immune receptors, including the TLR1–TLR2 heterodimer and TLR4, with WLaf1–TLR complexes showing relatively higher stability. Population coverage analysis indicated broad global applicability. Immune simulation analyses predicted robust humoral and cellular immune responses, with WLaf1 demonstrating predicted stronger antibody production, memory B-cell formation, and T-cell activation. Collectively, these computational findings suggest that both WLaf1 and WLaf2 represent potentially promising vaccine candidates against A. fumigatus, with WLaf1 exhibiting comparatively superior predicted performance. Further experimental and in vivo studies are required to validate the immunogenicity, safety, and protective efficacy of these vaccine candidates.
Tan et al. (Fri,) studied this question.