Immunogenic proteins of Orientia tsutsugamushi and implications for scrub typhus intervention: A narrative review

Abstract

Scrub typhus is an acute undifferentiated febrile infectious disease transmitted by a chigger (genus Leptotrombidium) bite carrying Orientia (O.) tsutsugamushi, affecting millions of people annually while more than one billion people are susceptible. Endemic areas are expanding to Africa, Europe, Middle East, and South America which is concerning, as despite best efforts, there is no vaccine to combat the bacteria. There are now three species of Orientia and over 20 strains of O. tsutsugamushi. The past attempts to develop a vaccine have been ineffective as they confer homologous strain-specific immunity. Various immunogenic proteins of O. tsutsugamushi have been identified that interact with the extracellular matrix (fibronectin) or vMLL5 receptor and modify the cytoskeleton of non-phagocytic host cells, which aids in host cell adhesion and invasion. These highly conserved proteins involve type specific antigen 56 (TSA56), 47 kDa, OmpA, and autotransporter proteins (ScaA, ScaB and ScaC). TSA56 is the most immunogenic and contains four types of hypervariable regions. Out of all autotransporter proteins, ScaA provides the homologous strains specific immunity and when coupled with TSA56 it shows better protective immunity against heterologous strains. The review provides detailed insight into the potential immunogenic proteins of Orientia which can be utilized to develop the vaccine. Furthermore, studies focused on highly antigenic proteins will provide more insight into their roles in developing therapeutics and easy-to-handle rapid diagnostic kits.

Keywords

Orientia tsutsugamushi / Immunogenic genes / Microbial pathogenesis / Vaccine / Scrub typhus

Conflict of interest statement

The authors declare no conflict of interest.

Acknowledgments

D.S. acknowledges Department of Health Research, Government of India for Young Scientist Fellowship. Authors duly acknowledge Central University of Himachal Pradesh for providing computational facilities.

Funding

This research was funded by Department of Health Research, Government of India, New Delhi, India (grant number: YSS/2020/000116/PRCYSS).

Authors’ contributions

Conceptualization, D.S. and S.K.; methodology, D.S. and A.S.; validation, S.S., A.R. and A.K.S.; formal analysis, A.S., R.K. and A.R.; investigation, S.S. and A.S.; data curation, D.S.; writing-original draft preparation, S.S.; writing-review and editing, D.S., A.S., S.K.; funding acquisition, D.S., S.K. All authors have read and agreed to the published version of the manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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