A pan-human coronavirus recombinant vaccine designed from conserved structural epitopes to counter emerging SARS-CoV-2 variants

Despite the global decline in COVID-19 incidence, approximately 50,000 active cases persist worldwide, and the continued emergence of immune-evasive SARS-CoV-2 variants, including BA.2.86 and JN.1, underscores the need for next-generation vaccines with broad and durable protection. In this study, we designed a recombinant multiepitope human coronavirus vaccine using an immunoinformatics-driven strategy to target conserved regions across structural proteins. Conserved antigenic regions within the spike (S), nucleocapsid (N), and membrane (M) proteins were identified from multiple SARS-CoV-2 variants. High-affinity T-cell and B-cell epitopes were selected and assembled into a recombinant vaccine construct (RVC) comprising four HLA class I-restricted epitopes, 27 HLA class II-restricted epitopes, and five linear B-cell epitopes. The RVC was predicted to provide extensive population coverage (99.99% globally and 99.80% in Asia) and demonstrated high antigenicity, non-allergenicity, and favorable physicochemical stability. Structural modelling revealed multiple conformational B-cell epitopes, and molecular docking showed stable interaction with Toll-like receptor 3 (TLR-3). Molecular dynamics simulations and MM-GBSA analysis estimated a favorable binding free energy (−5.19 kcal/mol) for the RVC–TLR-3 complex. Collectively, these findings support the RVC as a promising broad-spectrum human coronavirus vaccine candidate, warranting further experimental validation.