Immunoglobulin A (IgA) responses and IgE-associated inflammation along therespiratory tract after mucosal but not systemic immunization

The purpose of the present study was to determine the extent of immunologic responses, particularly immunopathologic responses, within the upper and l ower respiratory tracts after intranasal immunization using the mucosal adj uvant cholera toxin (CT). BALB/c mice were nasally immunized with influenza virus vaccine combined with CT. The inclusion of the mucosal adjuvant CT c learly enhanced generation of antibody responses in both the nasal passages and lungs. After nasal immunization, antigen specific immunoglobulin A (Ig A) antibody-forming cells dominated antibody responses throughout the respi ratory tract. However, IgG responses were significant in lungs but not in n asal passages. Furthermore, parenteral immunization did not enhance humoral immunity in the upper respiratory tract even after a nasal challenge, wher eas extrapulmonary lymphoid responses enhanced responses in the lung. After nasal immunization, inflammatory reactions, characterized by mononuclear c ell infiltration, developed within the lungs of mice but not in nasal passa ges. Lowering dosages of CT reduced, but did not eliminate, these adverse r eactions without compromising adjuvancy. Serum IgE responses were also enha nced in a dose-dependent manner by inclusion of CT. In summary, there are d ifferences in the generation of humoral immunity between the upper respirat ory tract and the lung. As the upper respiratory tract is in a separate com partment of the immune system from that stimulated by parenteral immunizati on, nasal immunization is an optimal approach to generate immunity througho ut the respiratory tract. Despite the promise of nasal immunization, there is also the potential to develop adverse immunopathologic reactions charact erized by pulmonary airway inflammation and IgE production.