title: Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA.
abstract: Mucosal immunisation may be used both to protect the mucosal surfaces against infections and as a means for immunological treatment of peripheral immunopathological disorders through the induction of systemic antigen-specific tolerance ('oral tolerance'). The development of mucosal vaccines, whether for prevention of infectious diseases or for oral tolerance immunotherapy, requires efficient antigen delivery and adjuvant systems that can help to present the appropriate vaccine or immunotherapy antigens to the mucosal immune system. The most potent (but also toxic) mucosal adjuvants are cholera toxin (CT) and the closely related Escherichia coli heat-labile enterotoxin (LT), and much effort and significant progress have been made recently to generate toxicologically acceptable derivatives of these toxins with retained adjuvant activity. Among these are the non-toxic, recombinantly produced cholera toxin B-subunit (CTB). CTB is a specific protective antigen component of a widely registered oral cholera vaccine as well as a promising vector for either giving rise to mucosal anti-infective immunity or for inducing peripheral anti-inflammatory tolerance to chemically or genetically linked foreign antigens administered mucosally. CT and CTB have also recently been used as combined vectors and adjuvants for markedly promoting ex vivo dendritic cell (DC) vaccination with different antigens and also steering the immune response to the in vivo-reinfused DCs towards either broad Th1 + Th2 + CTL immunity (CT) or Th2 or tolerance (CTB). Another type of mucosal adjuvants is represented by bacterial DNA or synthetic oligodeoxynucleotides containing CpG-motifs, which especially when linked to CTB have been found to effectively stimulate both innate and adaptive mucosal immune responses. The properties and clinical potential of these different classes of adjuvants are being discussed.
authors.affiliation: Department of Medical Microbiology & Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, P.O. Box 435, SE-40530 Göteborg, Sweden. jan.holmgren@microbio.gu.se
authors.forename: Jan
authors.initials: J
authors.lastname: Holmgren
authors.forename: Jenni
authors.initials: J
authors.lastname: Adamsson
authors.forename: Fabienne
authors.initials: F
authors.lastname: Anjuère
authors.forename: John
authors.initials: J
authors.lastname: Clemens
authors.forename: Cecil
authors.initials: C
authors.lastname: Czerkinsky
authors.forename: Kristina
authors.initials: K
authors.lastname: Eriksson
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Flach
authors.forename: Annie
authors.initials: A
authors.lastname: George-Chandy
authors.forename: Ali M
authors.initials: AM
authors.lastname: Harandi
authors.forename: Michael
authors.initials: M
authors.lastname: Lebens
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehner
authors.forename: Marianne
authors.initials: M
authors.lastname: Lindblad
authors.forename: Erik
authors.initials: E
authors.lastname: Nygren
authors.forename: Sukanya
authors.initials: S
authors.lastname: Raghavan
authors.forename: Joaquin
authors.initials: J
authors.lastname: Sanchez
authors.forename: Michael
authors.initials: M
authors.lastname: Stanford
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Sun
authors.forename: Ann-Mari
authors.initials: AM
authors.lastname: Svennerholm
authors.forename: Sara
authors.initials: S
authors.lastname: Tengvall
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001528:Behcet Syndrome / Q000276:immunology / Q000517:prevention & control; D002772:Cholera Toxin / Q000737:chemistry / Q000276:immunology*; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D014612:Vaccines; D002772:Cholera Toxin