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 histocompatibility complex (MHC) class II monoclonal antibodies (mAb) were used to immunize mice intranasally. Three weeks after intranasal (IN) priming, 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 worked much better than HEL alone in producing the secondary response. Control conjugates, containing an IgG isotype-matched mAb without specificity for mouse tissues, provided poor priming. Mice expressing MHC class II molecules, to which the anti-MHC II mAb could not bind, produced a weak antibody response compared with those that expressed the appropriate. MHC class II molecule. Our results demonstrate that immunotargeting to MHC class II molecules via the IN route allows priming of the local IgA and circulating IgG antibody, and indicate that this technique is a feasible approach for delivery of subunit vaccines in the upper respiratory tract.
Snider
D P
DP
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Underdown
B J
BJ
McDermott
M R
MR
D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D018796:Immunoconjugates / Q000008:administration & dosage*; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D007156:Immunologic Memory; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology; D017817:Nasal Lavage Fluid / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D000949:Histocompatibility Antigens Class II; D018796:Immunoconjugates; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D009113:Muramidase