title: Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA) vaccine to prevent anthrax in adults.
abstract: BACKGROUND
  The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA).
  
  
  RESULTS
  A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA.
  
  
  CONCLUSIONS
  The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00057525.
authors.affiliation: United States Military HIV Research Program, Henry M. Jackson Foundation, Rockville, Maryland, United States of America.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Brown
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.forename: Anita
authors.initials: A
authors.lastname: Gillis
authors.forename: Thomas C
authors.initials: TC
authors.lastname: VanCott
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.forename: Mark
authors.initials: M
authors.lastname: Milazzo
authors.forename: Tanya Santelli
authors.initials: TS
authors.lastname: Antonille
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.forename: Kelly T
authors.initials: KT
authors.lastname: McKee
authors.forename: Karen
authors.initials: K
authors.lastname: Metcalfe
authors.forename: Raburn M
authors.initials: RM
authors.lastname: Mallory
authors.forename: Deborah
authors.initials: D
authors.lastname: Birx
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
mesh_terms: D000293:Adolescent; D000328:Adult; D000881:Anthrax / Q000276:immunology* / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001408:Bacillus anthracis / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D004890:Erythema / Q000139:chemically induced; D004926:Escherichia coli / Q000235:genetics; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010146:Pain / Q000139:chemically induced; D011994:Recombinant Proteins / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D011994:Recombinant Proteins