A new TLR2 agonist promotes cross-presentation by mouse and human antigen presenting cells

作者：Santone Melissa; Aprea Susanna; Wu Tom Y H; Cooke Michael P; Mbow M Lamine; Valiante Nicholas M; Rush James S; Dougan Stephanie; Avalos Ana; Ploegh Hidde; De Gregorio Ennio; Buonsanti Cecilia^*; D'Oro Ugo

来源：Human Vaccines & Immunotherapeutics, 2015, 11(8): 2038-2050.

DOI：10.1080/21645515.2015.1027467

• B cells
• cross presentation
• priming
• cytotoxic T cells
• dendritic cells
• vaccination

Cross-presentation is the process by which professional APCs load peptides from an extracellularly derived protein onto class I MHC molecules to trigger a CD8(+) T cell response. The ability to enhance this process is therefore relevant for the development of antitumor and antiviral vaccines. We investigated a new TLR2-based adjuvant, Small Molecule Immune Potentiator (SMIP) 2.1, for its ability to stimulate cross-presentation. Using OVA as model antigen, we demonstrated that a SMIP2.1-adjuvanted vaccine formulation induced a greater CD8(+) T cell response, in terms of proliferation, cytokine production and cytolytic activity, than a non-adjuvanted vaccine. Moreover, using an OVA-expressing tumor model, we showed that the CTLs induced by the SMIP2.1 formulated vaccine inhibits tumor growth in vivo. Using a BCR transgenic mouse model we found that B cells could cross-present the OVA antigen when stimulated with SMIP2.1. We also used a flow cytometry assay to detect activation of human CD8(+) T cells isolated from human PBMCs of cytomegalovirus-seropositive donors. Stimulation with SMIP2.1 increased the capacity of human APCs, pulsed in vitro with the pp65 CMV protein, to activate CMV-specific CD8(+) T cells. Therefore, vaccination with an exogenous antigen formulated with SMIP2.1 is a successful strategy for the induction of a cytotoxic T cell response along with antibody production.

• 出版日期2015-8-3