IMMUNOINFORMATICS-GUIDED MULTI-EPITOPE VACCINE CANDIDATE DESIGN AND MHC DOCKING VALIDATION TARGETING THE GLYCOPROTEIN PRECURSOR OF THE NEWLY REPORTED ANDV/Switzerland/Hu-3337/2026 ORTHOHANTAVIRUS

The rapid release of viral genomic sequences allows early immunoinformatics screening before experimentally curated antigen information becomes available. In this study, the glycoprotein precursor (GP) of the newly reported ANDV/Switzerland/Hu-3337/2026 orthohantavirus was evaluated as a vaccine-design target using a stepwise workflow that integrated antigenicity prediction, conserved-region screening, transmembrane topology, MHC-I and MHC-II epitope prediction, peptide-construct design, and molecular docking against representative MHC receptors. The full GP sequence was predicted as a probable antigen by VaxiJen with a score of 0.5194. Conserved regions 1-50 and 81-240 were retained as antigenic regions and were located outside the predicted membrane-spanning helices. After filtering by MHC binding score and independent VaxiJen antigenicity, two CTL epitopes (VIYEKTHCV and KVKKTVLCY) and six HTL epitopes were selected. Four multi-epitope constructs (F1-F4) were generated using AAY and GPGPG linkers. Docking showed that F4 had the strongest MHC-I docking score (-226.92), whereas F2 had the strongest MHC-II docking score (-260.14). Residue contact-map analysis further indicated that the strongest complexes were supported by hydrogen bonds, salt bridges, alkyl/aliphatic contacts, and van der Waals interactions. These findings prioritize F2 and F4 as leading candidates for further three-dimensional refinement, molecular dynamics, allergenicity/toxicity filtering, population coverage, and experimental validation.