Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA.
The mucosal immune system consists of an integrated network of lymphoid cells that work in concert with innate host factors to promote host defence. Mucosal immunization can be used both to protect the mucosal surfaces against colonization and invasion by microbial pathogens and to provide a means for immunological treatment of selected autoimmune, allergic or infectious-immunopathological disorders through the induction of antigen-specific tolerance. The development of mucosal vaccines, whether for prevention of infectious diseases or for oral tolerance immunotherapy, requires efficient antigen delivery and adjuvant systems. Significant progress has recently been made to generate partly or wholly detoxified derivatives of cholera toxin (including the completely nontoxic cholera toxin B subunit) and the closely related Escherichia coli heat-labile enterotoxin, with retained adjuvant activity. Cholera toxin B subunit is a protective component of a widely registered oral vaccine against cholera, and has proven to be a promising vector for either giving rise to anti-infective immunity or for inducing peripheral anti-inflammatory tolerance to chemically or genetically linked foreign antigens administered mucosally. Promising advances have also recently been made in the design of efficient mucosal adjuvants based on bacterial DNA that contains CpG-motifs and various imidazoquinoline compounds binding to different Toll-like receptors on mucosal antigen-presenting cells.
Holmgren
Jan
J
Department of Medical Microbiology & Immunology, Göteborg University Vaccine Research Institute, Göteborg University, Sweden. jan.holmgren@microbio.gu.se
Harandi
Ali M
AM
Czerkinsky
Cecil
C
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000628:therapy; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D002771:Cholera / Q000276:immunology / Q000517:prevention & control; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000276:immunology; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D018928:Immunity, Mucosal; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D051193:Toll-Like Receptors; D014612:Vaccines / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; C472452:CpG-DNA, E coli; D004269:DNA, Bacterial; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014612:Vaccines; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli