title: Expansion and retention of pulmonary CD4+T cells after prime boost vaccination correlates with improved longevity and strength of immunity against tularemia.
abstract: Francisella tularensis subsp. tularensis strain SchuS4 (Ftt) is a highly virulent intracellular bacterium. Inhalation of 10 or fewer organisms results in an acute and potentially lethal disease called pneumonic tularemia. Ftt infections occur naturally in the U.S. and Ftt was developed as a bioweapon. Thus, there is a need for vaccines that protect against this deadly pathogen. Although a live vaccine strain of Francisella tularensis (LVS) exists, LVS fails to generate long-lived protective immunity against modest challenge doses of Ftt. We recently identified an important role for high avidity CD4+T cells in short-term protection and hypothesized that expanding this pool of cells would improve overall vaccine efficacy with regard to longevity and challenge dose. In support of our hypothesis, application of a prime/boost vaccination strategy increased the pool of high avidity CD4+T cells which correlated with improved survival following challenge with either increased doses of virulent Ftt or at late time points after vaccination. In summary, we demonstrate that both epitope selection and vaccination strategies that expand antigen-specific T cells correlate with superior immunity to Ftt as measured by survival.
authors.affiliation: Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA.
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Roberts
authors.affiliation: Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA.
authors.forename: Tara D
authors.initials: TD
authors.lastname: Wehrly
authors.affiliation: Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA.
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Crane
authors.affiliation: Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA. Electronic address: bosioc@niaid.nih.gov.
authors.forename: Catharine M
authors.initials: CM
authors.lastname: Bosio
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005604:Francisella tularensis / Q000276:immunology*; D007115:Immunization Schedule; D008168:Lung / Q000276:immunology*; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D014406:Tularemia / Q000276:immunology* / Q000517:prevention & control; D014481:United States
chemical_list: D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte
keywords: CD4(+) T cell; Francisella tularensis; High avidity T cell; Pulmonary immunity; Tularemia; Vaccine