Journal article
Inclusion of Epitopes That Expand High-Avidity CD4+ T Cells Transforms Subprotective Vaccines to Efficacious Immunogens against Virulent Francisella tularensis
The Journal of immunology (1950), Vol.197(7), pp.2738-2747
10/01/2016
DOI: 10.4049/jimmunol.1600879
PMCID: PMC5026927
PMID: 27543611
Abstract
T cells are the immunological cornerstone in host defense against infections by intracellular bacterial pathogens, such as virulent Francisella tularensis spp. tularensis (Ftt). The general paucity of novel vaccines for Ftt during the past 60 y can, in part, be attributed to the poor understanding of immune parameters required to survive infection. Thus, we developed a strategy utilizing classical immunological tools to elucidate requirements for effective adaptive immune responses directed against Ftt. Following generation of various Francisella strains expressing well-characterized lymphocytic choriomeningitis virus epitopes, we found that survival correlated with persistence of Ag-specific CD4(+) T cells. Function of these cells was confirmed in their ability to more effectively control Ftt replication in vitro. The importance of understanding the Ag-specific response was underscored by our observation that inclusion of an epitope that elicits high-avidity CD4(+) T cells converted a poorly protective vaccine to one that engenders 100% protection. Taken together, these data suggest that improved efficacy of current tularemia vaccine platforms will require targeting appropriate Ag-specific CD4(+) T cell responses and that elucidation of Francisella epitopes that elicit high-avidity CD4(+) T cell responses, specifically in humans, will be required for successful vaccine development.
Details
- Title: Subtitle
- Inclusion of Epitopes That Expand High-Avidity CD4+ T Cells Transforms Subprotective Vaccines to Efficacious Immunogens against Virulent Francisella tularensis
- Creators
- Lydia M Roberts - Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; andDeborah D Crane - Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; andTara D Wehrly - Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; andJoshua R Fletcher - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Bradley D Jones - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Catharine M Bosio - Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; and bosioc@niaid.nih.gov
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.197(7), pp.2738-2747
- DOI
- 10.4049/jimmunol.1600879
- PMID
- 27543611
- PMCID
- PMC5026927
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- Z01 AI001013-02 / Intramural NIH HHS HHSN272201300006C / NIAID NIH HHS
- Language
- English
- Date published
- 10/01/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083891602771
Metrics
14 Record Views