Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4⁺ T Cells with a Phenotype Distinct from That of Naïve PA T Cells

Cellular immune responses against protective antigen (PA) of Bacillus anthracis in subjects that received the anthrax vaccine adsorbed (AVA) vaccine were examined. Multiple CD4⁺ T-cell epitopes within PA were identified by using tetramer-guided epitope mapping. PA-reactive CD4⁺ T cells with a CD45RA⁻ phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (PBMC) with PA-specific tetramers. Surprisingly, PA-specific T cells were also detected in PBMC of nonvaccinees after a single cycle of in vitro PA stimulation. However, PA-reactive CD4⁺ T cells in nonvaccinees occurred at lower frequencies than those in vaccinees. The majority of PA-reactive T cells from nonvaccinees were CD45RA⁺ and exhibited a Th0/Th1 cytokine profile. In contrast, phenotyping and cytokine profile analyses of PA-reactive CD4⁺ T cells from vaccinees indicated that vaccination leads to commitment of PA-reactive T cells to a Th2 lineage, including generation of PA-specific, pre-Th2 central memory T cells. These results demonstrate that the current AVA vaccine is effective in skewing the development of PA CD4⁺ T cells to the Th2 lineage. The data also demonstrated the feasibility of using class II tetramers to analyze CD4⁺ cell responses and lineage development after vaccination.