title: The anthrax vaccine adsorbed vaccine generates protective antigen (PA)-Specific CD4+ T cells with a phenotype distinct from that of naive PA T cells.
abstract: Cellular immune responses against protective antigen (PA) of Bacillus anthracis in subjects that received the anthrax vaccine adsorbed (AVA) vaccine were examined. Multiple CD4(+) T-cell epitopes within PA were identified by using tetramer-guided epitope mapping. PA-reactive CD4(+) T cells with a CD45RA(-) phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (PBMC) with PA-specific tetramers. Surprisingly, PA-specific T cells were also detected in PBMC of nonvaccinees after a single cycle of in vitro PA stimulation. However, PA-reactive CD4(+) T cells in nonvaccinees occurred at lower frequencies than those in vaccinees. The majority of PA-reactive T cells from nonvaccinees were CD45RA(+) and exhibited a Th0/Th1 cytokine profile. In contrast, phenotyping and cytokine profile analyses of PA-reactive CD4(+) T cells from vaccinees indicated that vaccination leads to commitment of PA-reactive T cells to a Th2 lineage, including generation of PA-specific, pre-Th2 central memory T cells. These results demonstrate that the current AVA vaccine is effective in skewing the development of PA CD4(+) T cells to the Th2 lineage. The data also demonstrated the feasibility of using class II tetramers to analyze CD4(+) cell responses and lineage development after vaccination.
authors.affiliation: Benaroya Research Institute, Seattle, WA 98101, USA. bkwok@benaroyaresearch.org
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
authors.forename: Junbao
authors.initials: J
authors.lastname: Yang
authors.forename: Eddie
authors.initials: E
authors.lastname: James
authors.forename: John
authors.initials: J
authors.lastname: Bui
authors.forename: Laurie
authors.initials: L
authors.lastname: Huston
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Wiesen
authors.forename: Michelle
authors.initials: M
authors.lastname: Roti
mesh_terms: D022122:Anthrax Vaccines / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000037:antagonists & inhibitors; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*
chemical_list: D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; C030325:anthrax toxin; D017493:Leukocyte Common Antigens