title: Randomized clinical trial assessing the safety and immunogenicity of oral microencapsulated enterotoxigenic Escherichia coli surface antigen 6 with or without heat-labile enterotoxin with mutation R192G.
abstract: An oral, microencapsulated anti-colonization factor 6 antigen (meCS6) vaccine, with or without heat-labile enterotoxin with mutation R192G (LT(R192G)) (mucosal adjuvant), against enterotoxigenic Escherichia coli (ETEC) was evaluated for regimen and adjuvant effects on safety and immunogenicity. Sixty subjects were enrolled into a three-dose, 2-week interval or four-dose, 2-day interval regimen. Each regimen was randomized into two equal groups of meCS6 alone (1 mg) or meCS6 with adjuvant (2 microg of LT(R192G)). The vaccine was well tolerated and no serious adverse events were reported. Serologic response to CS6 was low in all regimens (0 to 27%). CS6-immunoglobulin A (IgA) antibody-secreting cell (ASC) responses ranged from 36 to 86%, with the highest level in the three-dose adjuvanted regimen; however, the magnitude was low. As expected, serologic and ASC LT responses were limited to adjuvanted regimens, with the exception of fecal IgA, which appeared to be nonspecific to LT administration. Further modifications to the delivery strategy and CS6 and adjuvant dose optimization will be needed before conducting further clinical trials with this epidemiologically important class of ETEC.
authors.affiliation: Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA. joyce.lapa@med.navy.mil
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Lapa
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Sincock
authors.forename: Madhumita
authors.initials: M
authors.lastname: Ananthakrishnan
authors.forename: Chad K
authors.initials: CK
authors.lastname: Porter
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Cassels
authors.forename: Carl
authors.initials: C
authors.lastname: Brinkley
authors.forename: Eric R
authors.initials: ER
authors.lastname: Hall
authors.forename: John
authors.initials: J
authors.lastname: van Hamont
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Gramling
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Carpenter
authors.forename: S
authors.initials: S
authors.lastname: Baqar
authors.forename: David R
authors.initials: DR
authors.lastname: Tribble
mesh_terms: D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C098406:CS6 antigen, E coli; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; C027538:heat-labile enterotoxin, E coli