title: The adjuvant effect of a non-toxic mutant of heat-labile enterotoxin of Escherichia coli for the induction of measles virus-specific CTL responses after intranasal co-immunization with a synthetic peptide.
abstract: The intranasal route has been shown to be effective for immunization. However, immunization via this route may require the use of potent and safe adjuvant. The construction of non-toxic mutants of heat labile enterotoxin of Escherichia coli (LT), which is a potent mucosal adjuvant, is a major breakthrough for the development of mucosal vaccines. In this study we have assessed the ability of an LT mutant (LTK63) to act as an adjuvant following intranasal co-immunization with a peptide corresponding to a measles virus cytotoxic T lymphocyte (CTL) epitope. LTK63 was more effective at potentiating the in vivo induction of peptide-specific and measles virus-specific CTL responses than was administration of the peptide in saline. A concentration of 10 micrograms/dose of LTK63 was found to be the most effective in potentiating the in vivo priming of peptide-specific and measles virus-specific CTL responses. These findings highlight the potential of the non-toxic mutant of LT as a safe mucosal adjuvant for use in humans.
authors.affiliation: Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, University of London, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Partidos
authors.forename: M
authors.initials: M
authors.lastname: Pizza
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: M W
authors.initials: MW
authors.lastname: Steward
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000235:genetics; D004768:Enterotoxins / Q000008:administration & dosage* / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D018928:Immunity, Mucosal; D007114:Immunization; D008213:Lymphocyte Activation; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D000939:Epitopes; D029968:Escherichia coli Proteins; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli