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

Abstract

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.

Keywords:

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

Funding

This work was supported in part by the Transformational Medical Technologies program contract HDTRA1-07-9-0001 from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA), European Union's seventh framework program grant code 280873 Advanced Immunization Technologies (ADITEC) and CTN01_00177_962865 grant from Ministero dell'Università e delle Ricerca (MIUR). M. S. was supported by an EMBO short term fellowship.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.