Development of a next generation pertussis vaccine: An unbiased biochemical approach to identify novel CD4+ T cell recognized antigens from Bordetella pertussis

Abstract

Abstract Waning acellular pertussis vaccine (aPV) efficacy has brought about the reemergence of pertussis despite global vaccine coverage. Decreasing vaccine efficacy is correlated with the emergence of vaccine escape mutants lacking bacterial antigens expressed in current laboratory strains. Recent work shows that systemic and mucosal CD4+ T cells are necessary for improved vaccine efficacy and increased duration of immunity. However, the antigens recognized by these T cells are undefined. We hypothesize that the efficacy and duration of aPV-induced immunity will be improved by the addition of new bacterial antigens that induce a strong CD4+ T cell response. Here we used the natural antigen processing machinery of mouse bone marrow derived dendritic cells to identify peptides derived from the laboratory Bp strain Bp536 and a clinical isolate, H762, that are presented on MHC Class II. Bioinformatics analysis selected the highest affinity peptides for both mice and human MHC Class II. The immunogenicity of each peptide was tested ex vivo using ELISA and an Activation Induced Marker (AIM) assay. We stimulated splenic T cells from convalescent or whole cell vaccine (wPV) immunized mice and human PBMCs. This unbiased biochemical approach generated a list of Bp-specific MHC Class II epitopes that are recognized by CD4+ T cells. These data suggest that Bp expresses multiple novel CD4+ T cell recognized antigens that may improve vaccine efficacy and the duration of protection when incorporated in a next generation aPV.