Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics.

TLR ligands are potent adjuvants and promote Th1 responses to coadministered Ags by inducing innate IL-12 production. We found that TLR ligands also promote the induction of IL-10-secreting regulatory T (Treg) cells through p38 MAPK-induced IL-10 production by dendritic cells (DC). Inhibition of p38 suppressed TLR-induced IL-10 and PGE(2) and enhanced IL-12 production in DC.

Innate IL-10 promotes the induction of Th2 responses with plasmid DNA expressing HIV gp120.

Like most DNA vaccines, intramuscular immunization with plasmid DNA coding for influenza virus haemagglutinin (HApDNA) induced Th1 responses and IgG2a antibodies in mice. However, plasmid DNA coding for HIV gp120 (gp120pDNA) induced Th2-biased responses and predominantly IgG1 antibodies. Responses to gp120pDNA switched to a Th1-type in IL-10-defective mice and to exclusively IgG2a antibodies in IL-4-defective mice.

In vivo phage display to identify M cell-targeting ligands.

Purpose: The purpose of this study was to use in vivo phage display screening technology to identify novel lead peptides that target delivery to M cells and to follicle-associated epithelium (FAE) of the intestine.

Methods: Phage display libraries were screened in vivo within the gastrointestinal tract of a rat model by successive screenings across four cycles of selection.

Results: Following four cycles of in vivo screening, we identified 30 unique peptide sequences that bound to Peyer's patch tissue, human Caco-2, and rat IEC-6 epithelial cells.