A library-selected, Langerhans cell-targeting peptide enhances an immune response

The ability to deliver antigens and immunomodulators specifically to Langerhans cells (LCs) in the skin could impact vaccine development. However, cell-specific targeting of therapeutic molecules remains a challenge in biomedicine. Using phage display technologies, we have developed a protocol that identifies peptides that mediate uptake into target cell types. Employing this approach, we have isolated a 20-mer peptide that mediates specific uptake by immunopotent LCs. The peptide is functional outside the context of the phage and is able to deliver a nanoparticle to LCs in vitro. Although selected on cells in vitro, the peptide is able to direct antigens and genes to LCs in vivo. Liposomes bearing the LC targeting peptide are able to deliver a transcriptionally active gene to LCs in a mouse model. Furthermore, we demonstrate that a low-dose injection into mice of phage bearing the LC-targeting peptide yields faster and higher immune responses against phage-associated antigens than control-phage injections.