Immunoinformatics approach to Rift Valley fever virus vaccine design in ruminants

Abstract

Introduction: Rift Valley fever (RVF) represents a significant public health challenge and economic burden due to its impact on livestock and potential to affect humans. Despite attempts to develop vaccines against the Rift Valley fever virus (RVFV), existing options are limited by concerns regarding the inability to differentiate between vaccinated and infected animals, vaccine-associated viremia, and the need for booster doses. This underscores the urgent need for a novel, effective, and safe vaccine, especially for use in ruminants, which this study seeks to address.

Methods: Employing reverse vaccinology—a cutting-edge approach combining bioinformatics and reverse pharmacology—we aimed to develop a novel RVFV vaccine. We focused on the M-glycoprotein segment, identifying highly conserved and immunodominant epitopes in viral glycoprotein sequences from cattle, sheep, and goats in RVF-endemic regions of Africa. Predictions for B- and T-cell epitopes were made, followed by the design of an epitope-based vaccine incorporating ideal linkers and a Bos taurus-specific beta-defensin to enhance immunogenicity. The vaccine's secondary and tertiary structures were analyzed using SOPMA and AlphaFold2, respectively.

Results: The vaccine candidate demonstrated promising physicochemical properties, with the M-glycoprotein sequences showing high antigenicity. Structural analysis revealed a composition of 31.55% alpha helices, 44.92% random coils, 5.35% beta turns, and 18.18% extended strands. Molecular docking with Toll-like receptors 7 and 8 indicated favorable molecular binding interactions, suggesting potential efficacy in stimulating an immune response.

Conclusion: This study paves the way for the development of a novel, safe RVFV vaccine. While the results are promising, further translational research is necessary to confirm the vaccine's effectiveness in animals and its applicability for improving public health outcomes.