Impact of Immunization Adjuvants and Sequences on the Induction of Antigen-Specific Regulatory T Cells 4784

Description It has been shown that unadjuvanted peptide vaccination generates a significant population of antigen-specific regulatory T (Treg) cells, while acute influenza virus infection and CpG adjuvant suppress their induction. However, in mice primed with an unadjuvanted vaccine, subsequent influenza virus infection led to an expansion of vaccine-specific Treg cells. Here, we investigated how immunization adjuvants and sequences influence Treg cell induction. We found that primary immunization with unadjuvanted peptide or adjuvanted with aluminum salt or MF59 induces a significant population of vaccine antigen-specific Treg cells. In contrast, acute influenza virus infection and CFA adjuvant suppressed their induction. Notably, in mice primed with unadjuvanted peptide, subsequent immunization with unadjuvanted peptide or alum further expanded vaccine-specific Treg cells, whereas MF59 or CFA adjuvant prevented their expansion. Interestingly, primary immunization with unadjuvanted or MF59-adjuvanted vaccine followed by influenza virus infection induced a significantly higher proportion of Treg cells compared to the reverse sequence. We also confirmed the suppressive function of MF59-induced Treg cells through in vitro and in vivo assays. In conclusion, our study shows that the immunization adjuvants and sequences significantly influence the induction and characteristics of antigen-specific Treg cells. These findings have important implications for optimizing vaccination strategies.