In silico antigenic and vaccinological characterization of two production-optimized recombinant yellow fever virus envelope proteins.

Abstract

Yellow fever virus (YFV) remains a major public health threat in Africa and South America. Although the live-attenuated 17D vaccine is highly effective, its use is restricted in certain vulnerable populations, emphasizing the need for nonreplicating alternatives. We performed an integrated in silico characterization of two production-optimized recombinant YFV envelope (Env) proteins derived from the Asibi and 17D strains. Physicochemical, antigenicity, solubility, allergenicity, epitope conservation, structural modeling, molecular docking, molecular dynamics (MD), electrostatic, and immune simulation analyses were conducted. Both proteins were predicted to be antigenic, hydrophilic, and structurally stable, although allergenicity predictions differed for 17D Env. Epitope mapping identified multiple predicted CD8⁺ and CD4⁺ T-cell epitopes, linear B-cell epitopes, and conformational antibody-accessible regions. T-cell epitopes showed substantial conservation across YFV strains, whereas linear B-cell epitopes exhibited greater variability. Structural comparisons supported conservation of the Env monomeric fold but revealed differences from experimentally determined dimeric assemblies, raising uncertainty regarding native quaternary organization and epitope accessibility. Docking and MD simulations with the neutralizing antibody YD6 identified predicted interactions and persistent intermolecular contacts. Immune simulations predicted coordinated adaptive responses following repeated immunization. Overall, these findings support further experimental evaluation of both recombinant Env proteins as potential nonreplicating vaccine antigens, diagnostic reagents, and tools for investigating YFV antigenicity and immune responses.

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