Extracellular vesicle-associated antigens as a new vaccine platform against scrub typhus.
Biochem Biophys Res Commun
; 523(3): 602-607, 2020 03 12.
Article
em En
| MEDLINE
| ID: mdl-31941602
Scrub typhus is an acute vector-borne disease caused by infection with the intracellular gram-negative bacterium Orientia tsutsugamushi (Ot). The rapid production of an efficient vaccine against Ot using novel strategies is required because of the global increase in mortality caused by these infections; however, no commercial vaccine is currently available. Ot induces T-cell-mediated immunogenic responses upon infection; therefore, a new rapidly producible vaccine that maximizes T-cell responses against Ot is required. In this study, we sought to develop a model vaccine platform for T-cell-mediated Ot infection using T-cell-immunity associated Salmonella-derived extracellular vesicles (EVs). For this purpose, we optimized DNA sequences encoding the full-length Ot proteins, TSA56, ScaA, ScaC, ScaD, and ScaE, and their expression in Salmonella. The sequences were incorporated into a new platform vector, pKST, which ectopically and concurrently produces Ot proteins and EVs. Expression analysis using pKST-antigen plasmids showed that TSA56 and ScaC produced antigen-associated EVs and showed strong T-cell immunogenic responses. We found that mice vaccinated with EVs derived from TSA56-expressing cells were protected from Salmonella-induced mortality. Therefore, our findings showed that Salmonella EV-associated antigen is a model platform for T-cell immune response infections. Our system could help prepare EV-antigen vaccines against scrub typhus in an easy and rapid manner.
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MEDLINE
Assunto principal:
Tifo por Ácaros
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Vacinas Bacterianas
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Vesículas Extracelulares
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Antígenos de Bactérias
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article