Design and evaluation of a multi-epitope subunit vaccine against human norovirus using an immunoinformatics approach

Objectives: This study aimed to identify safe, conserved, and highly immunogenic epitopes from all proteins of human-infecting norovirus (NoV) and to design a multi-epitope subunit vaccine construct from these epitopes using an immunoinformatics approach. Additionally, the vaccine construct was evaluated using both sequence-and structure-based assessments. Methods: Conserved fragments were identified from all proteins of human-infecting NoV, and B and T lymphocyte epitopes were subsequently predicted using multiple epitope prediction tools. The selected epitopes were linked to form a multi-epitope construct, incorporating various adjuvants in the design. Vaccine constructs with different adjuvants were analyzed for their physicochemical properties and immune simulation profiles, and the optimal combination was selected as the final vaccine candidate for further study. Finally, molecular docking and dynamics simulations were performed to visualize the interaction between the construct and a host immune receptor. Results: Twenty-two safe, conserved, and highly immunogenic epitopes were identified from all human-infecting NoV proteins. The construct adjuvanted with 50S ribosomal protein L7/ L12 (50SrpL7/L12) was chosen as the final vaccine candidate due to its optimal physicochemical properties and favorable immune simulation profile. Furthermore, the construct exhibited high binding affinity and a stable interaction with toll-like receptor 4). Conclusion: The multi-epitope subunit vaccine designed in this study shows promise as a potential NoV vaccine candidate for human immunization. Further in vitro and in vivo experiments are warranted to validate these findings.