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Vaccine. 2014 Feb 12;32(8):1019-28. doi: 10.1016/j.vaccine.2013.10.039. Epub 2013 Dec 25.

Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.

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Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States. Electronic address:
Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States.
Alabama Vaccine Research Clinic, University of Alabama at Birmingham, 908 20th Street South, Birmingham, AL 35294-2050, United States.
Walter Reed Army Institute for Research, 503 Robert Grant Avenue, Silver Springs, MD 20910-7500, United States.
Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States.
Mayo Clinic and Foundation, 611C Guggenheim Building, 200 First Street SW, Rochester, MN 55905, United States.
Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, United States.



We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired.


Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs).


The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at 42 months.


A priming series of 3 intramuscular doses administered at m0, m1, and m6 with a triennial booster was non-inferior to more complex schedules for achieving antibody response.



AE; AVA; AVRP; Adverse events; Anthrax Vaccine Research Program; Anthrax vaccines; Bacillus anthracis; Bacterial vaccines; CDC; Centers for Disease Control and Prevention; Department of Defense; DoD; FDA; Food and Drug Administration; GCP; Good Clinical Practices; IM; IND; Investigational New Drug; LTx; PA; SQ; USAMMA; United States Army Medical Materiel Agency; Vaccination; adverse event; anthrax vaccine adsorbed; intramuscularly; lethal toxin; protective antigen; subcutaneous

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