Vaccine development in Orientia tsutsugamushi infection

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Scrub typhus caused by O. tsutsugamushi is a re-emerging infection, causing significant morbidity and mortality in endemic areas. Disease severity range from mild, self-limiting illness to severe, even fatal illness -untreated mortality may reach 30-50%. Even under proper anti-microbial treatment, mortality may be as high 10% in severe cases. Hence, there is a great need for new treatment modalities in this disorder, including vaccines. Microbial and host factors are both determinants of outcome of dise ase and effectiveness of a vaccine, and we will adress the problems from both these angles. In order to develop broad-based and long-lasting protection against the different strains of O. tsutsugamushi, there is a need to further identify immunodominant a ntigens or their combinations. Also, the immune response to the particular agent must be determined, and success or failure of vaccines depends on the immune response they produce. Further elucidation of the most central immunopathogenic mechanisms in the development of O. tsutsugamushi infection is a prerequisite for development of vaccine. Further studies on the role of toll-like receptors, the homeostatic chemokines, regulatory T cells, and T and B cell interaction is of major importance for vaccine de velopment in O. tsutsugamushi infection. Several subunit vaccines against O. tsutsugamushi have been explored, particularly the 56kDa antigen, a strain specific, surface-exposed membrane protein, and the 47 kDa protein of O. tsutsugamushi, also a major an tigen in the outer membrane, have been promising. The project is part of a long-term strategic plan, studying immunopathogenic and microbial mechanisms in scrub typhus with the ambition to delineate new treatment modalities including a vaccine in this dis order. The combination of clinical and microbiologic expertise in India with the immunological expertise in Norway will be a major strength of the current project.