PMID- 24373307
OWN - NLM
STAT- MEDLINE
DCOM- 20140815
LR  - 20220716
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 32
IP  - 8
DP  - 2014 Feb 12
TI  - Effect of reduced dose schedules and intramuscular injection of anthrax vaccine 
      adsorbed on immunological response and safety profile: a randomized trial.
PG  - 1019-28
LID - S0264-410X(13)01415-1 [pii]
LID - 10.1016/j.vaccine.2013.10.039 [doi]
AB  - 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.
CI  - Published by Elsevier Ltd.
FAU - Wright, Jennifer G
AU  - Wright JG
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States. Electronic address: jgwright@cdc.gov.
FAU - Plikaytis, Brian D
AU  - Plikaytis BD
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Rose, Charles E
AU  - Rose CE
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Parker, Scott D
AU  - Parker SD
AD  - Alabama Vaccine Research Clinic, University of Alabama at Birmingham, 908 20th 
      Street South, Birmingham, AL 35294-2050, United States.
FAU - Babcock, Janiine
AU  - Babcock J
AD  - Walter Reed Army Institute for Research, 503 Robert Grant Avenue, Silver Springs, 
      MD 20910-7500, United States.
FAU - Keitel, Wendy
AU  - Keitel W
AD  - Departments of Molecular Virology & Microbiology and Medicine, Baylor College of 
      Medicine, One Baylor Plaza, Houston, TX 77030, United States.
FAU - El Sahly, Hana
AU  - El Sahly H
AD  - Departments of Molecular Virology & Microbiology and Medicine, Baylor College of 
      Medicine, One Baylor Plaza, Houston, TX 77030, United States.
FAU - Poland, Gregory A
AU  - Poland GA
AD  - Mayo Clinic and Foundation, 611C Guggenheim Building, 200 First Street SW, 
      Rochester, MN 55905, United States.
FAU - Jacobson, Robert M
AU  - Jacobson RM
AD  - Mayo Clinic and Foundation, 611C Guggenheim Building, 200 First Street SW, 
      Rochester, MN 55905, United States.
FAU - Keyserling, Harry L
AU  - Keyserling HL
AD  - Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, 
      United States.
FAU - Semenova, Vera A
AU  - Semenova VA
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Li, Han
AU  - Li H
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Schiffer, Jarad
AU  - Schiffer J
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Dababneh, Hanan
AU  - Dababneh H
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Martin, Sandra K
AU  - Martin SK
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Martin, Stacey W
AU  - Martin SW
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Marano, Nina
AU  - Marano N
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Messonnier, Nancy E
AU  - Messonnier NE
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
FAU - Quinn, Conrad P
AU  - Quinn CP
AD  - Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, 
      United States.
LA  - eng
SI  - ClinicalTrials.gov/NCT00119067
GR  - CC999999/ImCDC/Intramural CDC HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20131225
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Anthrax Vaccines)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Adult
MH  - Anthrax/*prevention & control
MH  - Anthrax Vaccines/*administration & dosage
MH  - Antibodies, Bacterial/blood
MH  - Antibody Formation
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - *Immunization, Secondary
MH  - Immunoglobulin G/blood
MH  - Injections, Intramuscular
MH  - Male
MH  - Middle Aged
PMC - PMC9067390
MID - NIHMS1798624
OTO - NOTNLM
OT  - AE
OT  - AVA
OT  - AVRP
OT  - Adverse events
OT  - Anthrax Vaccine Research Program
OT  - Anthrax vaccines
OT  - Bacillus anthracis
OT  - Bacterial vaccines
OT  - CDC
OT  - Centers for Disease Control and Prevention
OT  - Department of Defense
OT  - DoD
OT  - FDA
OT  - Food and Drug Administration
OT  - GCP
OT  - Good Clinical Practices
OT  - IM
OT  - IND
OT  - Investigational New Drug
OT  - LTx
OT  - PA
OT  - SQ
OT  - USAMMA
OT  - United States Army Medical Materiel Agency
OT  - Vaccination
OT  - adverse event
OT  - anthrax vaccine adsorbed
OT  - intramuscularly
OT  - lethal toxin
OT  - protective antigen
OT  - subcutaneous
COIS- Financial Disclosures No financial conflicts were reported for any author.
EDAT- 2014/01/01 06:00
MHDA- 2014/08/16 06:00
PMCR- 2022/05/04
CRDT- 2013/12/31 06:00
PHST- 2013/07/18 00:00 [received]
PHST- 2013/09/20 00:00 [revised]
PHST- 2013/10/08 00:00 [accepted]
PHST- 2013/12/31 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2014/08/16 06:00 [medline]
PHST- 2022/05/04 00:00 [pmc-release]
AID - S0264-410X(13)01415-1 [pii]
AID - 10.1016/j.vaccine.2013.10.039 [doi]
PST - ppublish
SO  - Vaccine. 2014 Feb 12;32(8):1019-28. doi: 10.1016/j.vaccine.2013.10.039. Epub 2013 
      Dec 25.