Targeting lymphocyte Peyer's patch adhesion molecule-1: a relay approach to gut immunization.
Targeting vaccines to dendritic cells (DCs) can enhance responses to weak vaccine antigens. Although there are molecules that are relatively specific for the various DC subsets, there are none that are both region-specific and DC-specific. This has provided some limitation to targeting regional DC populations. We proposed that these limits could be overcome by targeting antigens not to the DC subsets directly but to cells that persistently seek out and closely interact with DCs, namely lymphocytes. To investigate this hypothesis, we targeted antigens to a unique population of gut-homing lymphocytes and then looked at the induction of immune responses at this site. Using an anti-LPAM-1 (Lymphocyte Peyer's patch adhesion molecule-1; alpha(4)beta(7) integrin) monoclonal antibody (mAb) as a model antigen, we found that targeting gut-homing lymphocytes could significantly elevate the gut mucosal IgA response. Moreover, such a strategy greatly elevated the systemic IgG as well as IgA response. We found that LPAM-1-targeting enhanced the localization of antigen to both the systemic and mucosal lymphoid compartments where both IgA and IgG responses were induced. We also found that any parenteral route of delivery sufficed. Overall, targeting unique populations of lymphocytes may provide a strategy for ferrying antigen to sites that such lymphocytes home to.
McKenzie
Brent S
BS
The Walter and Eliza Hall Institute of Medical Research and Co-operative Research Centre for Vaccine Technology, PO Royal Melbourne Hospital, 1G Royal Parade, Parkville 3050, Australia.
Corbett
Alexandra J
AJ
Brady
Jamie L
JL
Boyle
Jefferey S
JS
Rockman
Steven P
SP
Lew
Andrew M
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D016023:Integrins / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D010581:Peyer's Patches / Q000276:immunology*; D051381:Rats
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016023:Integrins; C071777:integrin alpha4beta7