NOV 15, 2016 09:00 AM PST

Antigen-specific, poly-functional CD4+ T cells are required for vaccine-mediated protection in tularemia

Speakers
  • Rocky Mountain Laboratories, NIAID, NIH
    Biography
      Dr. Lydia Roberts received her undergraduate degrees in Chemistry and Biochemistry from Kansas State University in 2008 followed by her PhD in Microbiology and Immunology in 2013 from the University of North Carolina- Chapel Hill. Dr. Roberts is currently a post-doctoral fellow in the laboratory of Dr. Catharine Bosio at Rocky Mountain Laboratories, NIAID, NIH.

    Abstract:
    DATE: November 15, 2016
    TIME: 9:00 AM PT, 12:00 PM ET


    The virulent intracellular pathogen Francisella tularensis subsp. tularensis (Ftt) causes an acute, lethal disease called tularemia. Surviving tularemia depends on the presence of an effective adaptive immune response. However, the nature of such a response has not been elucidated. Thus, we designed in vitro and in vivo models to characterize the protective immune responses with the goal of applying these features to novel vaccines. Utilizing unlicensed vaccine strains with varying efficacy, we found that vaccinated mice lacking CD4+ T cells succumbed rapidly to Ftt challenge, surviving only 1 day longer than naïve animals. These data indicated that vaccine-mediated protection requires a pool of CD4+ T cells capable of immediately controlling Ftt replication. We found effective vaccination correlated with the presence of poly-functional CD4+ T cells producing IFN-γ, TNF-α, and IL-2 and these purified pulmonary and splenic CD4+ T cells controlled Ftt replication in vitro. To follow the antigen-specific response, we generated vaccine and Ftt strains expressing the well-characterized epitope gp61 from LCMV. Immune animals had persistent numbers of gp61-specific CD4+ T cells in their lymph nodes and spleens, whereas vaccinated, but non-immune animals did not. Therefore, we hypothesized the expansion of high avidity, antigen specific CD4+ T cells would convert a poorly efficacious vaccine to one that engenders protection. As predicted, inclusion of the gp61 epitope in both the vaccinating strain and virulent Ftt challenge strain converted a vaccine that failed evoke adequate T cell responses to one that was 100% protective. Together our work has revealed successful vaccines directed against an aggressive, highly pathogenic organism requires a large pool of high avidity, poly-functional CD4+ T cells. Moreover, the elucidation of Francisella epitopes that elicit high-avidity CD4+ T cell responses, specifically in humans, will be required for successful vaccine development

    Learning Objective 1: Learn about in vitro and in vivo immune response models to Francisella                                                 tularensis subsp. tularensis (Ftt) infection.

    Learning Objective 2: Learn how effective vaccination correlates with the presence of poly-                                                       functional CD4+ T cells.
     

    Show Resources
    You May Also Like
    MAY 24, 2018 09:30 AM PDT
    C.E. CREDITS
    MAY 24, 2018 09:30 AM PDT
    DATE: May 24, 2018 TIME: 9:30PM PDT The current gold standard in in vitro pre-clinical cancer treatment screening remain cell lines,...
    APR 27, 2018 10:00 AM PDT
    C.E. CREDITS
    APR 27, 2018 10:00 AM PDT
    DATE: April 27, 2018TIME: 10:00am PST, 1:00pm ESTGlioblastoma (GBM) and Medulloblastoma (MB) are the most common adult and paediatric brain tumours, both of which can have devastating c...
    AUG 15, 2018 08:00 AM PDT
    C.E. CREDITS
    AUG 15, 2018 08:00 AM PDT
    DATE: August 15, 2018TIME: 08:00AM PDT, 11:00AM EDTThe failure of current chemotherapeutic strategies in the fight against cancer can be largely attributed to the occurrence of drug res...
    JUN 29, 2018 09:00 AM PDT
    C.E. CREDITS
    JUN 29, 2018 09:00 AM PDT
    DATE: June 29, 2018TIME: 09:00AM PDT, 12:00PM EDT There is significant epidemiological evidence to suggest that the consumption of a high-broccoli diet is associated with a r...
    MAY 22, 2018 08:00 AM PDT
    C.E. CREDITS
    MAY 22, 2018 08:00 AM PDT
    DATE: May 22, 2018TIME: 08:00AM PDT The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that...
    MAY 29, 2018 09:00 AM PDT
    C.E. CREDITS
    MAY 29, 2018 09:00 AM PDT
    Recent advances in immuno-oncology research has proven the critical role of immune cells in cancer therapy. Deep understanding of the interaction and phenotype of immune and tumor cells withi...
    Loading Comments...