title: Preclinical evaluation of microencapsulated CFA/II oral vaccine against enterotoxigenic E. coli.
abstract: Colonization Factor Antigen (CFA/II) from enterotoxigenic Escherichia coli (ETEC) prepared under good manufacturing practices (GMP) was successfully incorporated into biodegradable poly(D,L-lactide-co-glycolide) (PLGA) polymer microspheres (BPM) under GMP and found to be safe and immunogenic when administered intraduodenally to rabbits. Following vaccination, Peyer's patch cells responded by lymphocyte proliferation to in vitro challenge with CFA/II. Also, B cells secreting specific anti-CFA/II antibodies were found in spleens following vaccination. No pathological changes were found following total necropsies of ten rabbits vaccinated with CFA/II BPM. Sixty-three per cent of the CFA/II BPM were between 5 and 10 microns diameter by volume particle size distribution; 1.17% protein content; 2.15% moisture; < 0.01% acetonitrile; 1.6% heptane; 22 non-pathogenic bacteria and three fungi per 1 mg protein dose; and passed the general safety test. We conclude that the CFA/II BPM oral vaccine is immunogenic and safe to begin a Phase I clinical safety study following Investigational New Drug approval.
authors.affiliation: Department of Gastroenterology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: R H
authors.initials: RH
authors.lastname: Reid
authors.forename: E C
authors.initials: EC
authors.lastname: Boedeker
authors.forename: C E
authors.initials: CE
authors.lastname: McQueen
authors.forename: D
authors.initials: D
authors.lastname: Davis
authors.forename: L Y
authors.initials: LY
authors.lastname: Tseng
authors.forename: J
authors.initials: J
authors.lastname: Kodak
authors.forename: K
authors.initials: K
authors.lastname: Sau
authors.forename: C L
authors.initials: CL
authors.lastname: Wilhelmsen
authors.forename: R
authors.initials: R
authors.lastname: Nellore
authors.forename: P
authors.initials: P
authors.lastname: Dalal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D001673:Biodegradation, Environmental; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D004386:Duodenum; D004926:Escherichia coli / Q000276:immunology*; D022361:Escherichia coli Vaccines; D036781:Fimbriae Proteins; D008213:Lymphocyte Activation; D008297:Male; D008863:Microspheres; D010581:Peyer's Patches / Q000276:immunology; D011098:Polyglactin 910 / Q000493:pharmacokinetics; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D022361:Escherichia coli Vaccines; C022924:colonization factor antigens; D036781:Fimbriae Proteins; D011098:Polyglactin 910