title: Safety and efficacy of E coli enterotoxin adjuvant for urease-based rectal immunization against Helicobacter pylori.
abstract: Low dose E. coli heat-labile enterotoxin (LT), delivered orally or enterically, has been used as an adjuvant for Helicobacter pylori (H. pylori) urease in healthy adults. In this study we aim to test the safety and adjuvant efficacy of LT delivered rectally together with recombinant H. pylori urease. Eighteen healthy adults without present or past H. pylori infection were enrolled in a double blind, randomized, ascending dose study to receive either urease (60 mg), or urease (60 mg) + LT (5 or 25 microg). The immunization preparation was administered per rectum on days 0, 14 and 28. Serum, stool and saliva anti-urease and anti-LT IgG and IgA antibodies (Abs) were measured and urease-specific and LT-specific antigen secreting cells (ASCs) were counted in peripheral blood at baseline and 7 (ASC counts) or 14 days (antibody levels) after each dosing. Peripheral blood lymphoproliferation assays were also performed at baseline and at the end of the study. Rectally delivered urease and LT were well tolerated. Among the 12 subjects assigned to urease+LT, 2 (16.7%) developed anti-urease IgG Abs, 1 (8.3%) developed anti-urease IgA Abs, and 3 (25%) showed urease-specific IgA(+) ASCs. Immune responses to LT were more vigorous, especially in subjects exposed to 5 microg LT. In the urease+ 5 microg LT group, anti-LT IgG and IgA Abs developed in 60 and 80% of the subjects, respectively, while LT-specific IgG(+) and IgA(+) ASCs were detected in all subjects. The magnitude of the anti-LT response was much higher than the response to urease. No IgA anti-urease or anti-LT Abs were detected in stool or saliva and lymphocyte proliferative responses to urease were unsatisfactory. In conclusion, rectal delivery of 5 microg LT is safe and induces vigorous systemic anti-LT immune responses. Further studies are needed to determine if LT can be an effective adjuvant for rectally delivered antigens.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Sougioultzis
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Lee
authors.forename: Mazen
authors.initials: M
authors.lastname: Alsahli
authors.forename: Subhas
authors.initials: S
authors.lastname: Banerjee
authors.forename: Michel
authors.initials: M
authors.lastname: Cadoz
authors.forename: Robert
authors.initials: R
authors.lastname: Schrader
authors.forename: Bruno
authors.initials: B
authors.lastname: Guy
authors.forename: Philip
authors.initials: P
authors.lastname: Bedford
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.forename: Ciaran P
authors.initials: CP
authors.lastname: Kelly
authors.forename: Pierre
authors.initials: P
authors.lastname: Michetti
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000285:Administration, Rectal; D000907:Antibodies, Bacterial / Q000097:blood; D004768:Enterotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000737:chemistry; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D012449:Safety; D014510:Urease / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D004768:Enterotoxins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014510:Urease