Bypassing luminal barriers, delivery to a gut addressin by parenteral targeting elicits local IgA responses.
Induction of mucosal immunity, particularly to subunit vaccines, has been problematic. The primary hurdle to successful mucosal vaccination is the effective delivery of vaccine antigen to the mucosal associated lymphoid tissue. Physical and chemical barriers restrict antigen access and, moreover, immune responses induced in the mucosa can be biased towards tolerance or non-reactivity. We proposed that these difficulties could be circumvented by targeting antigen to the gastrointestinal associated lymphoid tissue via systemic (parenteral) rather than alimentary routes, using antibodies specific for the mucosal addressin cellular adhesion molecule-1 (MAdCAM). After intravenous or intramuscular injection of such rat antibodies in mice, we found a greatly enhanced (up to 3 logs) anti-rat antibody response. MAdCAM targeting induces a rapid IgA antibody response in the gut and vastly improves the systemic antibody response. Targeting also enhanced T cell proliferation and cytokine responses. Parenteral targeting of mucosal addressins may represent a generic technique for bypassing mucosal barriers and eliminating the need for adjuvants in the induction of proximal and systemic immunity.
McKenzie
Brent S
BS
The Walter and Eliza Hall Institute of Medical Research and Co-operative Research Centre for Vaccine Technology, 1G Royal Parade, Parkville 3050, Australia.
Corbett
Alexandra J
AJ
Johnson
Susan
S
Brady
Jamie L
JL
Pleasance
Jill
J
Kramer
David R
DR
Boyle
Jefferey S
JS
Jackson
David C
DC
Strugnell
Richard A
RA
Lew
Andrew M
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D015815:Cell Adhesion Molecules; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology*; D051379:Mice; D009088:Mucoproteins / Q000276:immunology*; D009092:Mucous Membrane / Q000276:immunology; D051381:Rats; D014611:Vaccination
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007136:Immunoglobulins; C489082:Madcam1 protein, mouse; C504268:Madcam1 protein, rat; D009088:Mucoproteins