Musosal immunoadjuvant activity of recombinant Escherichia coli heat-labile enterotoxin and its B subunit: Induction of systemic IgG and secretory IgA responses in mice by intranasal immunization with influenza virus surface antigen

摘要: The Escherichia coli heat-labile enterotoxin (LT) is a very potent mucosal immunogen. LT also has strong adjuvant activity towards coadministered uni elated antigens and therefore of potential inter-est for development vaccines. However; despite the great demand such vaccines, use holotoxin us an essentially precluded by its toxicity. composed A subunit, carrying toxic ADP-ribosylation pentamer identical B subunits, which mediates binding to ganglioside G(M1), cellular receptor toxin. In this paper; we demonstrate that recombinant enzymatically inactive variants LT, including LTB itself; retain immunoadjuvant in murine influenza model. Mice were immunized intranasally (i.n.) with virus subunit antigen, consisting mostly isolated surface glycoprotein hemagglutinin (HA), supplemented either (rLTB), nontoxic mutant (E112K, Glu112-->Lys substitution subunit), or holotoxin, induction systemic IgG local S-IgA responses was evaluated direct enzyme-linked immunosorbent assay (ELISA). immunization antigen alone resulted poor response no detectable S-IgA. supplementation E112K rLTB substantial stimulation serum level nasal cavity. under these conditions same as holotoxin. present results particular; represent promising immunoadjuvants application i.n. vaccine. Nontoxic may be used vaccine formulations directed against other pathogens. respect, it interest LT(B)-stimulated antibody after observed at distant sites, urogenital system. This, principle, opens possibility develop vaccines sexually transmitted infectious diseases. (C) 1998 Elsevier Science Ltd. All rights reserved.