title: Boosting of post-exposure human T-cell and B-cell recall responses in vivo by Burkholderia pseudomallei-related proteins.
abstract: Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease with high incidence and mortality in South East Asia and northern Australia. To date there is no protective vaccine and antibiotic treatment is prolonged and not always effective. Most people living in endemic areas have been exposed to the bacteria and have developed some immunity, which may have helped to prevent disease. Here, we used a humanized mouse model (hu-PBL-SCID), reconstituted with human peripheral blood mononuclear cells from seropositive donors, to illustrate the potential of three known antigens (FliC, OmpA and N-PilO2) for boosting both T-cell and B-cell immune responses. All three antigens boosted the production of specific antibodies in vivo, and increased the number of antibody and interferon-γ-secreting cells, and induced antibody affinity maturation. Moreover, antigen-specific antibodies isolated from either seropositive individuals or boosted mice, were found to enhance phagocytosis and oxidative burst activities from human polymorphonuclear cells. Our study demonstrates that FliC, OmpA and N-PilO2 can stimulate human memory T and B cells and highlight the potential of the hu-PBL-SCID system for screening and evaluation of novel protein antigens for inclusion in future vaccine trials against melioidosis.
authors.affiliation: The Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Arnone
authors.initials: A
authors.lastname: Nithichanon
authors.affiliation: Department of Biosciences, University of Milan, Milan, Italy.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Gourlay
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: The Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ganjana
authors.identifier: 0000-0001-6972-585X
authors.initials: G
authors.lastname: Lertmemongkolchai
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D016957:Burkholderia pseudomallei / Q000276:immunology*; D002478:Cells, Cultured; D019353:Endemic Diseases; D036781:Fimbriae Proteins / Q000276:immunology; D005408:Flagellin / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008554:Melioidosis / Q000453:epidemiology / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D013785:Thailand
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D005408:Flagellin; D036781:Fimbriae Proteins; C078167:OMPA outer membrane proteins; D007371:Interferon-gamma
keywords: B cell; T cell; antibodies; memory; neutrophil