M cell targeting by a Claudin 4 targeting peptide can enhance mucosal IgA responses

BACKGROUND Mucosal immune surveillance is thought to be largely achieved through uptake by specialized epithelial M cells. We recently identified Claudin 4 as an M cell target receptor and developed a Claudin 4 targeting peptide (CPE) that can mediate uptake of nanoparticles through Nasal Associated Lymphoid Tissue (NALT) M cells. METHODS Recombinant influenza hemagglutinin (HA) and a version with the CPE peptide at the C-terminal end was used to immunize mice by the intranasal route along with a single dose of cholera toxin as an adjuvant. Serum and mucosal IgG and IgA responses were tested for reactivity to HA. RESULTS We found that the recombinant HA was immunogenic on intranasal administration, and inclusion of the CPE targeting peptide induced higher mucosal IgA responses. This mucosal administration also induced systemic serum IgG responses with Th2 skewing, but targeting did not enhance IgG responses, suggesting that the IgG response to mucosal immunization is independent of the effects of CPE M cell targeting. CONCLUSIONS M cell targeting mediated by a Claudin 4-specific targeting peptide can enhance mucosal IgA responses above the response to non-targeted mucosal antigen. Since Claudin 4 has also been found to be regulated in human Peyer's patch M cells, the CPE targeting peptide could be a reasonable platform delivery technology for mucosal vaccination.