title: Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial.
abstract: BACKGROUND
  In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).
  
  
  OBJECTIVE
  To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.
  
  
  METHODS
  Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).
  
  
  METHODS
  Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.
  
  
  METHODS
  Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.
  
  
  RESULTS
  At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.
  
  
  CONCLUSIONS
  The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Marano
authors.forename: Brian D
authors.initials: BD
authors.lastname: Plikaytis
authors.forename: Stacey W
authors.initials: SW
authors.lastname: Martin
authors.forename: Charles
authors.initials: C
authors.lastname: Rose
authors.forename: Vera A
authors.initials: VA
authors.lastname: Semenova
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Martin
authors.forename: Alison E
authors.initials: AE
authors.lastname: Freeman
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.forename: Scott D
authors.initials: SD
authors.lastname: Parker
authors.forename: Janiine
authors.initials: J
authors.lastname: Babcock
authors.forename: Wendy
authors.initials: W
authors.lastname: Keitel
authors.forename: Hana
authors.initials: H
authors.lastname: El Sahly
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobson
authors.forename: Harry L
authors.initials: HL
authors.lastname: Keyserling
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Soroka
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Fox
authors.forename: John L
authors.initials: JL
authors.lastname: Stamper
authors.forename: Michael M
authors.initials: MM
authors.lastname: McNeil
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Perkins
authors.forename: Nancy
authors.initials: N
authors.lastname: Messonnier
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Quinn
mesh_terms: D000328:Adult; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G