title: Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans.
abstract: Anthrax vaccine adsorbed (AVA), an effective countermeasure against anthrax, is administered as six subcutaneous (SQ) doses over 18 months. To optimize the vaccination schedule and route of administration, we performed a prospective pilot study comparing the use of fewer AVA doses administered intramuscularly (IM) or SQ with the current schedule and route. We enrolled 173 volunteers, randomized to seven groups, who were given AVA once IM or SQ; two doses, 2 or 4 weeks apart, IM or SQ; or six doses at 0, 2, 4 weeks and 6, 12, and 18 months (control group, licensed schedule and route). IM administration of AVA was associated with fewer injection site reactions than SQ administration. Following the first SQ dose of AVA, compared to males, females had a significantly higher rate of injection site reactions such as erythema, induration and subcutaneous nodules (P<0.001). Reaction rates decreased with a longer dose interval between the first two doses. The peak anti-PA IgG antibody response of subjects given two doses of AVA 4 weeks apart IM or SQ was comparable to that seen among subjects who received three doses of AVA at 2-week intervals. The IM route of administering this aluminum hydroxide adsorbed vaccine is safe and has comparable peak anti-PA IgG antibody levels when two doses are administered 4 weeks apart compared to the licensed initial dose schedule of three doses administered 2 weeks apart. A large pivotal study is being planned by the Centers for Disease Control and Prevention to confirm these results.
authors.affiliation: Division of Medicine, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702-5011, USA. phillip.pittman@det.amedd.army.mil
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Pittman
authors.forename: Gina
authors.initials: G
authors.lastname: Kim-Ahn
authors.forename: Dominique Y
authors.initials: DY
authors.lastname: Pifat
authors.forename: Kevin
authors.initials: K
authors.lastname: Coonan
authors.forename: Paul
authors.initials: P
authors.lastname: Gibbs
authors.forename: Steve
authors.initials: S
authors.lastname: Little
authors.forename: Judith G
authors.initials: JG
authors.lastname: Pace-Templeton
authors.forename: Robert
authors.initials: R
authors.lastname: Myers
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Parker
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Friedlander
mesh_terms: D000328:Adult; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010865:Pilot Projects; D011446:Prospective Studies; D012737:Sex Factors
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G