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

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.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.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.Most infectious agents enter the body through mucosal surfaces such as the intestine or airways. Protective immune responses induced by such infections involve both cellular immune responses and systemic IgG, but at mucosal surfaces secretory IgA provides the most effective protection. Studies have indicated that IgA responses are dependent on immune responses in mucosal lymphoid tissues such as intestinal Peyer's patches and Nasal Associated Lymphoid Tissues (NALT) or tonsils [1-4], where epithelial M cells acquire and transport antigens to underlying lymphoid tissue. Unfortunately, conventional vaccines rely instead on injected antigens, which induce IgG but not IgA. Live attenuated virus vaccines such as cold-adapted influenza (e.g., FluMist？), or oral polio vaccine can provide better mucosal immunity, but these are a greater challenge to develop, and they require an expensive cold chain that complicates delivery in developing countries.Vaccination at mucosal s