Exploring OmpA of Orientia tsutsugamushi to design novel multi-epitope vaccine against scrub typhus: an immunoinformatics approach.

Abstract

Scrub typhus is a commonly neglected infectious febrile illness caused by an obligate intracellular bacterium known as Orientia tsutsugamushi. It is a major health problem, affecting one million people annually, and poses threat to one billion people worldwide. There is always the escalating threat posed by the development of antibiotic resistance in the forthcoming future which emphasizes on urgency of the development of vaccine against Orientia tsutsugamushi. Despite eight decades of research and development, currently there is no viable vaccine available against scrub typhus. Outer membrane protein A (OmpA) is highly conserved and immunogenic across 51 geographically diverse isolates of Orientia tsutsugamishi. The multi-epitope vaccine was constructed by integrating four B-cell, four MHC-I, and four MHC-II epitopes linked together using specific linkers. The cholera enterotoxin subunit B is linked with the vaccine construct at N-terminal as an adjuvant. The constructed vaccine is 329 amino acid long, highly antigenic, non-allergen, non-toxic, soluble and has 36.3 kDa molecular weight. The molecular docking of vaccine construct with TLR receptors showed strong binding affinity. The interactions among vaccine and TLR receptors were analyzed using PDBsum. The in silico immune simulation of constructed vaccine showed ability to trigger immune response as shown by augmentation in T-cell and B-cell population. The current study provides the way forward for controlling the febrile disease scrub typhus.