Immunopharmacologsical and structural insights into Rift Valley fever virus envelope glycoproteins: an immunoinformatics approach to multi-epitope vaccine design.

Rift Valley fever (RVF) is a clinically zoonotic pathogen associated with severe systemic and neurological complications, for which no approved vaccine is currently available. This study aimed to design a novel chimeric multi-epitope vaccine candidate targeting the RVFV Envelope polyprotein (Gn and Gc) via an integrative immunoinformatic and structural modeling approach, targeting viral envelope glycoproteins which play a crucial role in host cell entry and immune recognition. The epitopes used in the vaccine assembly were selected on the basis of antigenicity, allergenicity, and toxicity, then linked to the RS09 adjuvant and optimized using linkers. The vaccine's 3D model was built using AlphaFold 3, and its potential to bind to the human TLR4 receptor (PDB ID: 4G8A) was investigated using ClusPro 2.0 docking. Population coverage and immune simulation were conducted using IEDB and the C-ImmSim server, respectively. The vaccine is highly antigenic, soluble, stable, and has a global population coverage of more than 90%. In addition, the vaccine was found to be effective as indicated by a high binding energy and good complementarity to the complex formed by the TLR4 receptor. This study demonstrates that a highly effective and safe vaccine candidate for global RVF prevention is feasible and should be considered for development.