PMID- 26979136
OWN - NLM
STAT- MEDLINE
DCOM- 20161011
LR  - 20181113
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 34
IP  - 18
DP  - 2016 Apr 19
TI  - Randomized, double-blind, active-controlled study evaluating the safety and 
      immunogenicity of three vaccination schedules and two dose levels of AV7909 
      vaccine for anthrax post-exposure prophylaxis in healthy adults.
PG  - 2096-105
LID - S0264-410X(16)00284-X [pii]
LID - 10.1016/j.vaccine.2016.03.006 [doi]
AB  - AV7909 vaccine being developed for post-exposure prophylaxis of anthrax disease 
      may require fewer vaccinations and reduced amount of antigen to achieve an 
      accelerated immune response over BioThrax((R)) (Anthrax Vaccine Adsorbed). A phase 
      2, randomized, double-blind, BioThrax vacccine-controlled study was conducted to 
      evaluate the safety and immunogenicity of three intramuscular vaccination 
      schedules and two dose levels of AV7909 in 168 healthy adults. Subjects were 
      randomized at a 4:3:2:4:2 ratio to 5 groups: (1) AV7909 on Days 0/14; (2) AV7909 
      on Days 0/28; (3) AV7909 on Days 0/14/28; (4) half dose AV7909 on Days 0/14/28; 
      and (5) BioThrax vaccine on Days 0/14/28. Vaccinations in all groups were well 
      tolerated. The incidences of adverse events (AEs) were 79% for AV7909 subjects 
      and 65% for BioThrax subjects; 92% of AV7909 subjects and 87% of BioThrax 
      subjects having AEs reported Grade 1-2 AEs. No serious AEs were assessed as 
      potentially vaccine-related, and no AEs of potential autoimmune etiology were 
      reported. There was no discernible pattern indicative of a safety concern across 
      groups in the incidence or severity of reactogenicity events. Groups 2-4 achieved 
      success for the primary endpoint, demonstrated by a lower 95% confidence limit of 
      the percentage of subjects with protective toxin neutralizing antibody NF50 
      values (>/=0.56) to be >/=40% at Day 63. Group 1 marginally missed the criterion 
      (lower bound 95% confidence limit of 39.5%). Immune responses were above this 
      threshold for Groups 1, 3 and 4 at Day 28 and all groups at Day 42. Further study 
      of an AV7909 two-dose schedule given 2 weeks apart is warranted in light of the 
      favorable tolerability profile and immunogenicity response relative to three 
      doses of BioThrax vaccine, as well as preliminary data from nonclinical studies 
      indicating similar immune responses correlate with higher survival for AV7909 
      than BioThrax vaccine.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Hopkins, Robert J
AU  - Hopkins RJ
AD  - Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA. 
      Electronic address: hopkinsr@ebsi.com.
FAU - Kalsi, Gurdyal
AU  - Kalsi G
AD  - Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA.
FAU - Montalvo-Lugo, Victor M
AU  - Montalvo-Lugo VM
AD  - Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA.
FAU - Sharma, Mona
AU  - Sharma M
AD  - Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA.
FAU - Wu, Yukun
AU  - Wu Y
AD  - Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA.
FAU - Muse, Derek D
AU  - Muse DD
AD  - Jean Brown Research, 1045 East 3900 South, Suite 100, Salt Lake City, UT 84124, 
      USA.
FAU - Sheldon, Eric A
AU  - Sheldon EA
AD  - Miami Research Associates, 6141 Sunset Drive, Suite 301, South, Miami, FL 33143, 
      USA.
FAU - Hampel, Frank C
AU  - Hampel FC
AD  - Central Texas Health Research, 705-A Landa, New Braunfels, TX 78130, USA.
FAU - Lemiale, Laurence
AU  - Lemiale L
AD  - Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA.
LA  - eng
GR  - HHSN272201000035C/AI/NIAID NIH HHS/United States
GR  - HHSN272201000035C/PHS HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20160312
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Anthrax Vaccines)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Biothrax)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (ProMune)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Adult
MH  - Anthrax/*prevention & control
MH  - Anthrax Vaccines/administration & dosage/adverse effects/*therapeutic use
MH  - Antibodies, Bacterial/blood
MH  - Antibodies, Neutralizing/blood
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - *Immunization Schedule
MH  - Male
MH  - Middle Aged
MH  - Oligodeoxyribonucleotides/administration & dosage
MH  - Post-Exposure Prophylaxis/*methods
MH  - Young Adult
PMC - PMC4839983
MID - NIHMS771229
OTO - NOTNLM
OT  - Anthrax
OT  - BioThrax((R)) (Anthrax Vaccine Adsorbed)
OT  - CPG 7909
OT  - Post-exposure prophylaxis
OT  - Vaccine
EDAT- 2016/03/17 06:00
MHDA- 2016/10/12 06:00
PMCR- 2017/04/19
CRDT- 2016/03/17 06:00
PHST- 2015/12/03 00:00 [received]
PHST- 2016/02/15 00:00 [revised]
PHST- 2016/03/03 00:00 [accepted]
PHST- 2016/03/17 06:00 [entrez]
PHST- 2016/03/17 06:00 [pubmed]
PHST- 2016/10/12 06:00 [medline]
PHST- 2017/04/19 00:00 [pmc-release]
AID - S0264-410X(16)00284-X [pii]
AID - 10.1016/j.vaccine.2016.03.006 [doi]
PST - ppublish
SO  - Vaccine. 2016 Apr 19;34(18):2096-105. doi: 10.1016/j.vaccine.2016.03.006. Epub 
      2016 Mar 12.