Bypassing luminal barriers, delivery to a gut addressin by parenteral targeting elicits local IgA responses
- Author(s)
- McKenzie, BS; Corbett, AJ; Johnson, S; Brady, JL; Pleasance, J; Kramer, DR; Boyle, JS; Jackson, DC; Strugnell, RA; Lew, AM;
- Details
- Publication Year 2004-11,Volume 16,Issue #11,Page 1613-1622
- Journal Title
- INTERNATIONAL IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- MUCOSAL VASCULAR ADDRESSIN; CELL-ADHESION MOLECULE-1; CD8(+) T-CELLS; IMMUNE-SYSTEM; ORAL TOLERANCE; LYMPH-NODE; VACCINE; ANTIGEN; IMMUNIZATION; INDUCTION
- Publisher's Version
- https://doi.org/10.1093/intimm/dxh163
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-11-01 12:00:00