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