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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.

Author information

1
Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States. Electronic address: jgwright@cdc.gov.
2
Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States.
3
Alabama Vaccine Research Clinic, University of Alabama at Birmingham, 908 20th Street South, Birmingham, AL 35294-2050, United States.
4
Walter Reed Army Institute for Research, 503 Robert Grant Avenue, Silver Springs, MD 20910-7500, United States.
5
Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States.
6
Mayo Clinic and Foundation, 611C Guggenheim Building, 200 First Street SW, Rochester, MN 55905, United States.
7
Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, United States.

Abstract

OBJECTIVE:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00119067.

KEYWORDS:

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

PMID:
24373307
DOI:
10.1016/j.vaccine.2013.10.039
[Indexed for MEDLINE]

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