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Hum Vaccin Immunother. 2015;11(8):2038-50. doi: 10.1080/21645515.2015.1027467.

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

Author information

1
a Novartis Vaccines and Diagnostics s.r.l. (a GlaxoSmithKline Company) ; Siena , Italy.

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:

APC, antigen presenting cell; B cells; BCR, B cell receptor; CMV, cytomegalovirus; CTL, cytotoxic t lymphocyte; DC, dendritic cell; HCMV, human CMV; KO, knock out; LN, lymph node; MHC, major histocompatibility complex; OVA, avalbumin; PBMC, peripheral blood mononuclear cell; SMIP, Small Molecule Immune Potentiator; TLR, toll like receptor; cross presentation/priming; cytotoxic T cells; dendritic cells; vaccination

PMID:
26024409
PMCID:
PMC4635931
DOI:
10.1080/21645515.2015.1027467
[Indexed for MEDLINE]
Free PMC Article

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