Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA

• 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. © 2004 Elsevier B.V. All rights reserved.

Nyckelord

Anti-immunopathology

Anti-infection

Mucosal adjuvants

antigen

bacterial DNA

BCG vaccine

cancer antibody

cholera b subunit whole cell cholera vaccine

cholera toxin

cholera toxin a subunit

cholera toxin B subunit

cholera vaccine

CpG DNA

dendritic cell vaccine

enterotoxin

immunostimulating agent

immunosuppressive agent

influenza vaccine

ISCOM

oligodeoxynucleotide derivative

peptide derivative

tetanus toxin

unclassified drug

virus vector

adjuvant therapy

allergic reaction

antigen specificity

autoimmune disease

bacterial infection

Behcet disease

cholera

conference paper

dendritic cell

drug delivery system

drug safety

drug tolerability

Escherichia coli

ex vivo study

genital system

human

Human immunodeficiency virus infection

immune response

immune system

immunization

immunopathogenesis

immunopathology

immunotherapy

in vivo study

infection

influenza

influenza vaccination

innate immunity

mucosal immunity

nonhuman

priority journal

protein motif

side effect

Th1 cell

Th2 cell

tumor

uveitis

vaccination

virus infection

*Adjuvants

Immunologic

Animals

Behcet Syndrome/immunology/prevention & control

Cholera Toxin/chemistry/*immunology

CpG Islands/genetics/*immunology

Humans

Immunity

Mucosal/immunology

Vaccines/*immunology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)