Mucosal immunogenicity and adjuvant activity of the recombinant A subunit of the Escherichia coli heat-labile enterotoxin
| Autor: | De Haan, L, Holtrop, M, Verweij, W R, Agsteribbe, E, Wilschut, J |
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| Přispěvatelé: | Groningen University Institute for Drug Exploration (GUIDE) |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
G(M1)-BINDING ACTIVITY
Bacterial Toxins VIBRIO-CHOLERAE Immunoglobulins Antibodies Viral Enterotoxins Mice Adjuvants Immunologic Escherichia coli Animals KEYHOLE LIMPET HEMOCYANIN INTRANASAL IMMUNIZATION TOXIN-B-SUBUNIT Antigens Viral Immunity Mucosal Administration Intranasal RIBOSYLATION ACTIVITY Mice Inbred BALB C Escherichia coli Proteins CHOLERA-TOXIN ADP-RIBOSYLTRANSFERASE ACTIVITY Original Articles respiratory system Antibodies Bacterial Recombinant Proteins carbohydrates (lipids) NONTOXIC MUTANT Influenza B virus stomatognathic diseases Immunoglobulin A Secretory lipids (amino acids peptides and proteins) ORAL IMMUNIZATION |
| Zdroj: | Immunology, 97(4), 706-713. Wiley-Blackwell |
| Popis: | The Escherichia coti heat-labile enterotoxin (LT) is an exceptionally effective mucosal immunogen and mucosal immunoadjuvant towards coadministered antigens. Although, in general, the molecular basis of these properties is poorly understood, both the toxic ADP-ribosylation activity of the LTA subunit and the cellular toxin receptor, ganglioside, G(M1)-binding properties of the LTB-pentamer have been suggested to be involved. In recent studies we found that G(M1)-binding is not essential for the adjuvanticity of LT, suggesting an important role for the LTA subunit in immune stimulation. We now describe the immunomodulatory properties of recombinant LTA molecules with or without ADP-ribosylation activity, LTA(His)(10) and LTA-E112K(His)(10), respectively. These molecules were expressed as fusion proteins with an N-terminal His-tag to allow simple purification on nickel-chelate columns. Their immunogenic and immunoadjuvant properties were assessed upon intranasal administration to mice, and antigen-specific serum immunoglobulin-isotype and -subtype responses and mucosal secretory immunoglobulin A (IgA) responses were monitored using enzyme-linked immunosorbent assay. With respect to immunogenicity, both LTA(His)(10) and LTA-E112K(His)(10) failed to induce antibody responses. On the other hand, immunization with both LT and the non-toxic LT-E112K mutant not only induced brisk LTB-specific, but also LTA-specific serum and mucosal antibody responses. Therefore, we conclude that linkage of LTA to the LTB; pentamer is essential for the induction of LTA-specific responses. With respect to adjuvanticity, both LTA(His)(10) and LTA-E112K(His)(10) were found to stimulate serum and mucosal antibody responses towards coadministered influenza subunit antigen. Remarkably, responses obtained with LTA(His)(10) were comparable in both magnitude and serum immunoglobulin isotype and subtype distributions to those observed after communization with LT, LT-E112K, or recombinant LTB. We conclude that LTA, by itself can act as a potent adjuvant for intranasally administered antigens in a fashion independent of ADP-ribosylation activity and association with the LTB pentamer. |
| Databáze: | OpenAIRE |
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