Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial.
BACKGROUND
In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).


OBJECTIVE
To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.


METHODS
Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).


METHODS
Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.


METHODS
Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.


RESULTS
At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.


CONCLUSIONS
The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.
Marano
Nina
N
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Plikaytis
Brian D
BD
Martin
Stacey W
SW
Rose
Charles
C
Semenova
Vera A
VA
Martin
Sandra K
SK
Freeman
Alison E
AE
Li
Han
H
Mulligan
Mark J
MJ
Parker
Scott D
SD
Babcock
Janiine
J
Keitel
Wendy
W
El Sahly
Hana
H
Poland
Gregory A
GA
Jacobson
Robert M
RM
Keyserling
Harry L
HL
Soroka
Stephen D
SD
Fox
Sarah P
SP
Stamper
John L
JL
McNeil
Michael M
MM
Perkins
Bradley A
BA
Messonnier
Nancy
N
Quinn
Conrad P
CP
D000328:Adult; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G