Ravi Sharma,
Author Of 1 Presentation
IDENTIFICATION AND CHARACTERIZATION OF ANTIGEN-SPECIFIC CD4+ T CELL EPITOPES THAT ACTIVATE MARKED HUMAN TH1 AND TH17 CELL RESPONSES FOR NEW VACCINE DEVELOPMENT AGAINST PNEUMOCOCCAL INFECTION (ID 1147)
Abstract
Background
Streptococcus pneumoniae(Spn) is a leading cause of invasive bacterial diseases. Despite the use of polysaccharide-based vaccines, Spn remains a major cause of invasive disease due to reasons including the increase in non-vaccine serotypes. Recent efforts focus on the development of protein-based vaccines for broad immunity. Previous studies showed that CD4+ T cells particularly Th17 cells are critical in host clearance of Spn and we showed domain 4 pneumolysin(D4Ply) activated CD4+ T cells including Th17 which were inversely associated with Spn carriage.
Methods
We now examined CD4+ T cell epitopes from D4Ply that activate Th17/Th1 cells in nasopharynx-associated lymphoid tissue(NALT) from children and adults. A number of peptides spanning whole length D4Ply were tested for capacity to activate T cells by cell proliferation (CFSE staining), intracellular cytokine staining and cytokine array.
Results
We identified several immunodominant epitopes that activated marked Th1/Th17 responses in NALT and PBMC, as demonstrated by intracellular cytokine staining and increased IFNg and IL17A levels in cell culture. CD4+ T cell proliferative response and cytokine production activated by peptide pools could be enhanced by an adjuvant Endocine.
Conclusions
Identification of immuno-dominant CD4+ T cell epitopes eliciting marked Th17 response offers great potential for peptides-based vaccine against pneumococcal infection in humans.