Computational design of a glycosylated multi-epitope vaccine against HAsV-1 and HAsV-2 astrovirus for acute gastroenteritis

Human astrovirus (HAsVs) is a significant viral agent responsible for acute gastroenteritis, primarily affecting children. Among HAsVs serotypes, HAsVs − 1 and HAsVs-2 are the most virulent serotypes, contributing to severe gastrointestinal infections, and having limited therapeutics. This study aims to design multi-epitope vaccine candidate with predicted glycosylation sites against HAsVs-1 and HAsVs-2 utilizing an immunoinformatic approach. B-cell and T-cell epitopes in which natural glycan sites were present were selected and linked via GPGPG, AAY, and KK linkers, with an adjuvant to stimulate a balanced immune response. The 3D structure of the vaccine was validated via Ramachandran plot, following molecular docking with human immune receptors, and then subjected to dual molecular dynamics (MD) simulations via AMBER and DESMOND to confirm interaction stability and to predict its immunogenic profile. The HAsVs vaccine demonstrated strong immunogenic properties, including more than 70% of global populations, with favorable physiochemical characteristics, including an antigenicity score of 0.534, instability index of 29.26, molecular weight of 24,230.71 Da, and GRAVY score of − 0.126, ensuring stability, solubility, and hydrophilicity. Molecular docking studies confirmed stable binding with human immune receptors, particularly with HLA-DR, showing a binding energy of − 272.83 kcal/mol, and 35 hydrogen bonds. In MD simulations, the RMSD reached a stable point at ~ 15–20 Å (Desmond) and ~ 1.5 Å (AMBER), indicating little movement. RMSF values were mainly less than 8 Å, with flexible parts around residues 50 and 150. The radius of Gyration (Rg) stabilized around 33.0–26.0 Å (Desmond) and ~ 5 Å (AMBER), confirming the compactness. Immune simulation predicted a strong, Th1-dominated response, with antigen concentrations peaking at nearly 700,000 antigens per mL, and IFN-γ levels reaching approximately 450,000 ng/mL, supporting effective adaptive immunity with minimal Th2 activation. Although this research is an in-silico study, the results demonstrate the strong potential of a multi-epitope vaccine candidate against HAsVs.