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Integrating core subtractive proteomics and reverse vaccinology for multi-epitope vaccine design against Rickettsia prowazekii endemic typhus

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Abstract

Rickettsia prowazekii is an intracellular, obligate, gram-negative coccobacillus responsible for epidemic typhus. Usually, the infected body louse or its excrement when rubbed into the skin abrasions transmits the disease. The infection with R. prowazekii causes the highest death rate (> 20% without antibiotic treatment and now 1–7%), followed by epidemic typhus, which often manifests in unsanitary conditions (up to 15–30%). Conventionally, vaccine design has required pathogen growth and both assays (in vivo and in vitro), which are costly and time-consuming. However, advancements in bioinformatics and computational biology have accelerated the development of effective vaccine designs, reducing the need for traditional, time-consuming laboratory experiments. Subtractive genomics and reverse vaccinology have become prominent computational methods for vaccine model construction. Therefore, the RefSeq sequence of Rickettsia prowazekii (strain Madrid E) (Proteome ID: UP000002480) was subjected to subtractive genomic analysis, including factors such as non-similarity to host proteome, essentiality, subcellular localization, antigenicity, non-allergenicity, and stability. Based on these parameters, the vaccine design process selected specific proteins such as outer membrane protein R (O05971_RICPR PETR; OmpR). Eventually, the OmpR was subjected to a reverse vaccinology approach that included molecular docking, immunological simulation, and the discovery of B-cell epitopes and MHC-I and MHC-II epitopes. Consequently, a chimeric or multi-epitope-based vaccine was proposed by selecting the V11 vaccine and its 3D structure modeling along with molecular docking against TLR and HLA protein, in silico simulation, and vector designing. The obtained results from this investigation resulted in a new perception of inhibitory ways against Rickettsia prowazekii by instigating novel immunogenic targets. To further assess the efficacy and protective ability of the newly designed V11 vaccine against Rickettsia prowazekii infections, additional evaluation such as in vitro or in vivo immunoassays is recommended.

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All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

The authors would like to acknowledge the Higher Education Commission of Pakistan for providing financial support under National Research Program for Universities.

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Authors and Affiliations

  1. Department of Biotechnology, University of Karachi, Karachi, Pakistan

    Ariba Khan & Muhammad Hassan Khanzada

  2. Lab 103, PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Ariba Khan, Muhammad Hassan Khanzada, Kanwal Khan & Reaz Uddin

  3. HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

    Khurshid Jalal

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Correspondence to Reaz Uddin.

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Khan, A., Khanzada, M.H., Khan, K. et al. Integrating core subtractive proteomics and reverse vaccinology for multi-epitope vaccine design against Rickettsia prowazekii endemic typhus. Immunol Res 72, 82–95 (2024). https://doi.org/10.1007/s12026-023-09415-y

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