INTRANASAL ANTIGEN TARGETING TO MHC CLASS-II MOLECULES PRIMES LOCAL IGA AND SERUM IGG ANTIBODY-RESPONSES IN MICE

Covalent conjugates of hen egg lysozyme (HEL) and anti-major histocomp atibility complex (MHC) class II monoclonal antibodies (mAb) were used to immunize mice intranasally. Three weeks after intranasal (IN) prim ing, mice responded rapidly to IN challenge with a mixture of HEL and cholera toxin (CT), by producing large titres of anti-HEL IgA and IgG1 antibody in serum, and IgA antibody in nasal secretions. No secondary response to HEL plus CT occurred in mice that received no priming or mice primed with HEL alone. The secondary serum IgG antibody response was dominated by the IgG1 subclass. HEL combined with CT adjuvant work ed much better than HEL alone in producing the secondary response. Con trol conjugates, containing an IgG isotype-matched mAb without specifi city for mouse tissues, provided poor priming. Mice expressing MHC cla ss II molecules, to which the anti-MHC II mAb could not bind, produced a weak antibody response compared with those that expressed the appro priate MHC class II molecule. Our results demonstrate that immunotarge ting to MHC class II molecules via the IN route allows priming of the local IgA and circulating IgG antibody, and indicate that this techniq ue is a feasible approach for delivery of subunit vaccines in the uppe r respiratory tract.