Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.
Vaccine
; 32(8): 1019-28, 2014 Feb 12.
Article
in En
| MEDLINE
| ID: mdl-24373307
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.Key words
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
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunization, Secondary
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Anthrax Vaccines
/
Anthrax
Type of study:
Clinical_trials
Limits:
Adult
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Vaccine
Year:
2014
Document type:
Article