Route for Inducing Protective Immunity Eye Mucosa: An Efficient Vaccine Delivery

The external part of the eye shares mucosa-associated common characteristics and is an obvious entry site for foreign Ags. We assessed the potential of eyedrop vaccination for effective delivery of vaccines against viral or bacterial infection in mice. Both OVA-specific IgG Ab in serum and IgA Ab in mucosal compartments were induced by eyedrops of OVA with cholera toxin (CT). Eyedrop vaccination of influenza A/PR/8 virus (H1N1) induced both influenza virus-specific systemic and mucosal Ab responses and protected mice completely against respiratory infection with influenza A/PR/8 virus. In addition, eyedrop vaccination of attenuated Salmonella vaccine strains induced LPS-specific Ab and complete protection against oral challenge of virulent Salmonella. Unlike with the intranasal route, eyedrop vaccinations did not redirect administered Ag into the CNS in the presence of CT. When mice were vaccinated by eyedrop, even after the occlusion of tear drainage from eye to nose, Ag-specific systemic IgG and mucosal IgA Abs could be induced effectively. Of note, eyedrops with OVA plus CT induced organogenesis of conjunctiva-associated lymphoid tissue and increased microfold cell-like cells on the conjunctiva-associated lymphoid tissue in the nictitating membrane on conjunctiva, the mucosal side of the external eye. On the basis of these findings, we propose that the eyedrop route is an alternative to mucosal routes for administering vaccines. A vaccine that induces an immune response by fortifying mucosal immunity is an effective way of targeting the pathogen before infection occurs (1, 2). Mucosal vaccination , in contrast to parenteral vaccination, is of particular interest because it can elicit both systemic and mucosal immune responses, mainly secretory IgA (sIgA) Abs, at the very portal of entry of most infectious pathogens (3). Vaccine development has lagged behind the rapidity of disease propagation in the era of global travel. Mu-cosal vaccination, which is easy to administer and does not require special training, has become a strategy to thwart new pathogen strains before they become pandemic. The eye mucosa is a possible route for mucosal vaccine because it is an important entry point for environmental Ags and infectious materials occupying most of the external ocular surface (4–6). The conjunctiva, part of the eye mucosa, has immunologic features in common with other mucosal tissues. The conjunctiva has CD8 + T cells in the epithelium, equal proportions of CD4 + and CD8 + T cells, B cells, and mast cells in the lamina propria, and dendritic cells (DCs) and Langerhans cells …