title: Discovery of a protective Rickettsia prowazekii antigen recognized by CD8+ T cells, RP884, using an in vivo screening platform.
abstract: Rickettsia prowazekii has been tested for biological warfare due to the high mortality that it produces after aerosol transmission of very low numbers of rickettsiae. Epidemic typhus, the infection caused by these obligately intracellular bacteria, continues to be a threat because it is difficult to diagnose due to initial non-specific symptoms and the lack of commercial diagnostic tests that are sensitive and specific during the initial clinical presentation. A vaccine to prevent epidemic typhus would constitute an effective deterrent to the weaponization of R. prowazekii; however, an effective and safe vaccine is not currently available. Due to the cytoplasmic niche of Rickettsia, CD8(+) T-cells are critical effectors of immunity; however, the identification of antigens recognized by these cells has not been systematically addressed. To help close this gap, we designed an antigen discovery strategy that uses cell-based vaccination with antigen presenting cells expressing microbe's proteins targeted to the MHC class I presentation pathway. We report the use of this method to discover a protective T-cell rickettsial antigen, RP884, among a test subset of rickettsial proteins.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Michal
authors.initials: M
authors.lastname: Gazi
authors.forename: Erika
authors.initials: E
authors.lastname: Caro-Gomez
authors.forename: Yenny
authors.initials: Y
authors.lastname: Goez
authors.forename: Maria A
authors.initials: MA
authors.lastname: Cespedes
authors.forename: Marylin
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Paula
authors.initials: P
authors.lastname: Correa
authors.forename: Gustavo
authors.initials: G
authors.lastname: Valbuena
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D019295:Computational Biology; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D005822:Genetic Vectors / Q000378:metabolism; D051379:Mice; D015203:Reproducibility of Results; D012283:Rickettsia prowazekii / Q000235:genetics / Q000276:immunology*; D012290:Rickettsial Vaccines / Q000276:immunology; D014438:Typhus, Epidemic Louse-Borne / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D012290:Rickettsial Vaccines