Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii

作者：Fizza Arshad, Asifa Sarfraz, Muhammad Shehroz, Umar Nishan, Asia Perveen, Riaz Ullah, Mohamed Akhiruddin Ibrahim, Mohibullah Shah · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-024-83395-3 · 被引用次数：8 · 研究领域：vaccines and immunoinformatics approaches、Vector-borne infectious diseases、Antimicrobial Peptides and Activities

Rocky Mountain Spotted Fever, caused by the gram-negative intracellular bacteria Rickettsia rickettsii, is a serious tick-borne infection with a fatality rate of 20-30%, if not treated. Since it is the most serious rickettsial disease in North America, modified prevention and treatment strategies are of critical importance. In order to find new therapeutic targets and create multiepitope vaccines, this study integrated subtractive proteomics with reverse vaccinology. The core genome of R. rickettsii was investigated, resulting in the identification of seven essential, human non-homologous proteins as potential drug targets, as well as four antigenic, non-allergenic proteins suitable for vaccine development. Using conserved antigenic peptides, two chimeric vaccine constructs were developed and assessed using molecular docking, molecular dynamics simulations, principal component analysis, MM-GBSA binding free energy, and dynamic cross-correlation matrix studies. The high immunogenic potential was indicated by the vaccine designs' robust and consistent interactions with human immunological receptors. Their capacity to trigger strong humoral and cellular immunological responses was further demonstrated by in silico immune simulations. The persistent interactions of vaccine V1 and V2 with human immunological receptor demonstrated that these might have high immunogenic potential. Moreover, the identified drug targets were annotated for essential biological processes, which shed lig...