Development of an in vitro system for screening adjuvant combinations for induction of specific patterns of CD4 T cell differentiation (VAC10P.967)

Abstract

Abstract Adjuvants are a critical component of many vaccines, but their mechanisms of action remain poorly understood. While great progress has been made in defining several pathways that are activated by various adjuvants, their impact on adaptive immunity remains largely unpredictable. Here, we developed an experimental system to screen multiple defined compounds with known adjuvant activity on the strength and quality of antigen-specific murine CD4 T cell priming in vitro. By screening combinations of suboptimal concentrations of 30 adjuvants, we identified combinations that showed remarkable synergy in priming naive CD4 T cells toward TH1, TH2, TH17 or TfH phenotypes. By applying a variety of computational algorithms to data from this in vitro approach, we identified synergy between agonists of different pattern recognition receptor families for induction of specific functional programs in CD4 T cells during priming. These were ranked by strength of polarization and with respect to robustness under different culture conditions. Immunizations in mice showed strong correlations between in vitro ranking and in vivo outcomes of antigen specific CD4 T cell responses. Our approach provides a method for analyzing large numbers of adjuvant combinations to predict their influence on the outcome of CD4 T cell priming in vivo. This should assist in the development of new adjuvants that enable more predictable and functionally polarized CD4 T cell responses following vaccination.