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Bypassing luminal barriers, delivery to a gut addressin by parenteral targeting elicits local IgA responses

McKenzie, Brent S., Corbett, Alexandra J., Johnson, Susan, Brady, Jamie L., Pleasance, Jill, Kramer, David, Boyle, Jefferey S., Jackson, David C., Strugnell, Richard A. and Lew, Andrew M. 2004, Bypassing luminal barriers, delivery to a gut addressin by parenteral targeting elicits local IgA responses, International immunology, vol. 16, no. 11, pp. 1613-1622, doi: 10.1093/intimm/dxh163.

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Title Bypassing luminal barriers, delivery to a gut addressin by parenteral targeting elicits local IgA responses
Author(s) McKenzie, Brent S.
Corbett, Alexandra J.
Johnson, Susan
Brady, Jamie L.
Pleasance, Jill
Kramer, David
Boyle, Jefferey S.
Jackson, David C.
Strugnell, Richard A.
Lew, Andrew M.
Journal name International immunology
Volume number 16
Issue number 11
Start page 1613
End page 1622
Publisher Oxford University Press
Place of publication Oxford, England
Publication date 2004-10-05
ISSN 0953-8178
1460-2377
Keyword(s) adhesion molecules
antigen targeting
mucosa
vaccination
Summary 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.
Language eng
DOI 10.1093/intimm/dxh163
Field of Research 110799 Immunology not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2004, Japanese Society for Immunology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30008692

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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