Milk IgA responses are augmented by antigen delivery to the mucosal addressin cellular adhesion molecule 1.
The mucosal addressin cellular adhesion molecule 1 (MAdCAM) is expressed on the venules of the gut associated lymphoid tissue (GALT); it is also expressed on the venules of the lobules of the mammary gland. We have previously found that MAdCAM-targeting using a rat anti-MAdCAM monoclonal Ab as both antigen and targeting moiety resulted in an enhanced local IgA gut response. We therefore surmised that such targeting may also enhance IgA responses in the mammary gland. We show that our model antigen localizes to the lobules of the mammary glands as well as the GALT, but not to the draining lymph nodes and that targeting MAdCAM results in secretory IgA responses in the milk. We provide evidence that this milk IgA Ab is of a secretory nature and is consistent with derivation from gut plasmablasts that have migrated to the mammary gland. Targeting MAdCAM may be a way for a novel vaccine strategy that affords protection to the mammary gland and the suckling neonate.
Johnson
Susan
S
The Walter and Eliza Hall Institute of Medical Research and the Co-operative Research Centre for Vaccine Technology, 1G Royal Parade, Parkville 3050, Vic., Australia.
Bourges
Dorothee
D
Wijburg
Odilia
O
Strugnell
Richard A
RA
Lew
Andrew M
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007774:Lactation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D008321:Mammary Glands, Animal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008892:Milk / Q000276:immunology*; D009088:Mucoproteins; D011247:Pregnancy; D051381:Rats; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007071:Immunoglobulin A, Secretory; C489082:Madcam1 protein, mouse; D009088:Mucoproteins