Effect of reduced dose schedules and intramuscular injection of anthrax vaccine
adsorbed on immunological response and safety profile: a randomized trial.
Author(s): Wright JG(1), Plikaytis BD(2), Rose CE(2), Parker SD(3), Babcock J(4), Keitel
W(5), El Sahly H(5), Poland GA(6), Jacobson RM(6), Keyserling HL(7), Semenova
VA(2), Li H(2), Schiffer J(2), Dababneh H(2), Martin SK(2), Martin SW(2), Marano
N(2), Messonnier NE(2), Quinn CP(2).
Affiliation(s): 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.
Publication date & source: 2014, Vaccine. , 32(8):1019-28
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.
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