Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii
Abstract 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 stra...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-83395-3 |
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| author | Fizza Arshad Asifa Sarfraz Muhammad Shehroz Umar Nishan Asia Perveen Riaz Ullah Mohamed A. Ibrahim Mohibullah Shah |
| author_facet | Fizza Arshad Asifa Sarfraz Muhammad Shehroz Umar Nishan Asia Perveen Riaz Ullah Mohamed A. Ibrahim Mohibullah Shah |
| author_sort | Fizza Arshad |
| collection | DOAJ |
| description | Abstract 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 light on their therapeutic potential. The vaccine constructs were cloned and expressed in suitable systems. This study displays a comprehensive strategy for managing Rocky Mountain Spotted Fever via rational vaccine development. Further experimental research is needed to confirm the immunogenicity of the vaccines and the druggability of identified targets, establishing the path toward effective RMSF management. |
| format | Article |
| id | doaj-art-c88d1e916be041c79a51cd16c0481971 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c88d1e916be041c79a51cd16c04819712025-01-12T12:15:15ZengNature PortfolioScientific Reports2045-23222025-01-0115112510.1038/s41598-024-83395-3Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsiiFizza Arshad0Asifa Sarfraz1Muhammad Shehroz2Umar Nishan3Asia Perveen4Riaz Ullah5Mohamed A. Ibrahim6Mohibullah Shah7Department of Biochemistry, Bahauddin Zakariya UniversityDepartment of Biochemistry, Bahauddin Zakariya UniversityDepartment of Bioinformatics, Kohsar University MurreeDepartment of Chemistry, Kohat University of Science & TechnologySchool of Natural Sciences, Faculty of Science and Engineering, Macquarie UniversityDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutics, College of Pharmacy, King Saud UniversityDepartment of Biochemistry, Bahauddin Zakariya UniversityAbstract 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 light on their therapeutic potential. The vaccine constructs were cloned and expressed in suitable systems. This study displays a comprehensive strategy for managing Rocky Mountain Spotted Fever via rational vaccine development. Further experimental research is needed to confirm the immunogenicity of the vaccines and the druggability of identified targets, establishing the path toward effective RMSF management.https://doi.org/10.1038/s41598-024-83395-3Immunoinformaticsreverse vaccinologydrug pocketbinding energyBrazilian spotted fever |
| spellingShingle | Fizza Arshad Asifa Sarfraz Muhammad Shehroz Umar Nishan Asia Perveen Riaz Ullah Mohamed A. Ibrahim Mohibullah Shah Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii Scientific Reports Immunoinformatics reverse vaccinology drug pocket binding energy Brazilian spotted fever |
| title | Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii |
| title_full | Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii |
| title_fullStr | Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii |
| title_full_unstemmed | Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii |
| title_short | Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii |
| title_sort | core genome guided novel therapeutic targets identification and chimeric vaccine designing against rickettsia rickettsii |
| topic | Immunoinformatics reverse vaccinology drug pocket binding energy Brazilian spotted fever |
| url | https://doi.org/10.1038/s41598-024-83395-3 |
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