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ADP-ribosylating enterotoxins as vaccine adjuvants

Journal article
Authors Nils Y Lycke
Cristina Lebrero-Fernandez
Published in Current opinion in pharmacology
Volume 41
Pages 42-51
ISSN 1471-4892
Publication year 2018
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 42-51
Language en
Links https://www.ncbi.nlm.nih.gov/pubmed...
Keywords 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
Subject categories Immunology in the medical area

Abstract

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.

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