ADP-ribosylating enterotoxins as vaccine adjuvants

• Most infections are caused by pathogens that access the body at mucosal sites. Hence, development of mucosal vaccines to prevent local infection or invasion of pathogens appears highly warranted, especially since only mucosal immunization will stimulate strong local IgA responses and tissue resident memory CD4 and CD8 T cells. The most significant obstacle to developing such vaccines is the lack of approved adjuvants that can effectively and safely enhance relevant mucosal and systemic immune responses. The most potent mucosal adjuvants known today are the adenosine diphosphate (ADP)-ribosylating bacterial enterotoxins cholera toxin (CT) and Escherichia coli heat-labile toxins (LTs). Unfortunately, these molecules are also very toxic, which precludes their clinical use. However, much effort has been devoted to developing derivatives of these enterotoxins with low or no toxicity and retained adjuvant activity. Although it is fair to say that we know more about how these toxins affect the immune system than ever before, we still lack a detailed understanding of how and why these toxins are effective adjuvants. In the present review, we provide a state-of-the-art overview of the mechanism of action of the holotoxins and the strategies used for improving the toxin-based adjuvants.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

adenosine diphosphate ribosylation factor 6

B7 antigen

CD40 antigen

CD86 antigen

chemokine receptor CCR4

chemokine receptor CCR7

CXCL13 chemokine

cyclic AMP

cyclic AMP responsive element binding protein

cystic fibrosis transmembrane conductance regulator

enterotoxin

gamma interferon

ganglioside GM1

guanine nucleotide binding protein

immunological adjuvant

interferon consensus sequence binding protein

interleukin 10

interleukin 12

interleukin 17

interleukin 23

interleukin 4

interleukin 5

interleukin 6

major histocompatibility antigen class 2

nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase

nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase A1

nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase A2

STAT3 protein

unclassified drug

adenosine diphosphate ribosylation

cellular immunity

conformational transition

disulfide bond

endocytosis

endoplasmic reticulum

endoplasmic reticulum associated degradation

enzyme activity

enzyme conformation

Escherichia coli

humoral immunity

lymphocyte differentiation

nonhuman

priority journal

protein binding

protein cleavage

protein expression

protein protein interaction

Review

Th1 cell

Th17 cell

Th2 cell

upregulation

Vibrio cholerae

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)