Abstract
ABSTRACT Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Despite the wide range of approaches explored during the last seventy years, an effective prophylactic vaccine is not yet available. Here, we developed a novel recombinant antigen derived from conserved regions of 56 kDa type-specific antigen (TSA56), a major outer membrane protein responsible for genetic heterogeneity and antigenicity, and evaluated it as a protective vaccine antigen. Our findings demonstrate that immunization with conserved blocks of TSA56 (cTSA56) not only provides protective immunity against lethal challenges with the homologous genotype, but also confers significantly better protection against heterologous genotypes than TSA56. Adoptive transfer of CD4+ or CD8+ T cells from immunized mice provided significantly enhanced protection against lethal challenge, whereas immune B cells failed to do so, indicating that cellular immunity against the conserved epitopes plays a protective role. Moreover, immunization with a 10-mer peptide mixture, screened from CD8+ T cell epitopes within the conserved region of TSA56, provided enhanced protection against lethal challenge with O. tsutsugamushi. Therefore, this novel recombinant antigen is a promising candidate for scrub typhus vaccine against a wide range of O. tsutsugamushi genotypes.
Highlights
Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi, an obligate intracellular bacterium
Vaccination with a 39 peptide mixture selected by CD8+ T cell epitope screening conferred significantly better protection against bacterial challenge than non-immune control. These results indicate that conserved blocks of TSA56 (cTSA56) is a promising candidate for scrub typhus vaccine against a wide range of O. tsutsugamushi genotypes
To characterize the variation of tsa56 genes, we defined conserved blocks (CBs) and variable blocks (VBs) based on amino acid sequences by Gblocks software
Summary
Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Clinical manifestations begin with an eschar at the site of mite feeding and regional lymphadenopathy, followed by fever, headache, myalgia, and rash. Disease mortality of untreated patients has been estimated to be approximately 6.0% with a wide range (min–max) of 0–70% [2]. Even though the endemic region of scrub typhus is geographically confined to the Asia-Pacific area [3], there has recently been a new emergence in South America and Africa [4]. It has been estimated that more than a million cases occur annually within the endemic region; the rapid increase of scrub typhus incidence and sporadic outbreaks makes it an emerging public health issue [3]
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