PMID- 27155494
OWN - NLM
STAT- MEDLINE
DCOM- 20171215
LR  - 20181113
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 34
IP  - 51
DP  - 2016 Dec 12
TI  - Evaluation of early immune response-survival relationship in cynomolgus macaques 
      after Anthrax Vaccine Adsorbed vaccination and Bacillus anthracis spore 
      challenge.
PG  - 6518-6528
LID - S0264-410X(16)30202-X [pii]
LID - 10.1016/j.vaccine.2016.04.048 [doi]
AB  - Anthrax Vaccine Adsorbed (AVA, BioThrax) is approved by the US Food and Drug 
      Administration for post-exposure prophylaxis (PEP) of anthrax in adults. The PEP 
      schedule is 3 subcutaneous (SC) doses (0, 14 and 28 days), in conjunction with a 
      60 day course of antimicrobials. The objectives of this study were to understand 
      the onset of protection from AVA PEP vaccination and to assess the potential for 
      shortening the duration of antimicrobial treatment 
      (http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf). We 
      determined the efficacy against inhalation anthrax in nonhuman primates (NHP) of 
      the first two doses of the PEP schedule by infectious challenge at the time 
      scheduled for receipt of the third PEP dose (Day 28). Forty-eight cynomolgus 
      macaques were randomized to five groups and vaccinated with serial dilutions of 
      AVA on Days 0 and 14. NHP were exposed to Bacillus anthracis Ames spores on Day 
      28 (target dose 200 LD(50) equivalents). Anti-protective antigen (PA) IgG and 
      toxin neutralizing antibody (TNA) responses to vaccination and in post-challenge 
      survivors were determined. Post-challenge blood and selected tissue samples were 
      assessed for B. anthracis at necropsy or end of study (Day 56). Pre-challenge 
      humoral immune responses correlated with survival, which ranged from 24 to 100% 
      survival depending on vaccination group. Surviving, vaccinated animals had 
      elevated anti-PA IgG and TNA levels for the duration of the study, were 
      abacteremic, exhibited no apparent signs of infection, and had no gross or 
      microscopic lesions. However, survivors had residual spores in lung tissues. We 
      conclude that the first two doses of the PEP schedule provide high levels of 
      protection by the scheduled timing of the third dose. These data may also support 
      consideration of a shorter duration PEP antimicrobial regimen.
CI  - Copyright A(c) 2016 Elsevier Ltd. All rights reserved.
FAU - Sivko, G S
AU  - Sivko GS
AD  - Battelle Memorial Institute, Columbus, OH 43201, USA. Electronic address: 
      sivkog@battelle.org.
FAU - Stark, G V
AU  - Stark GV
AD  - Battelle Memorial Institute, Columbus, OH 43201, USA.
FAU - Tordoff, K P
AU  - Tordoff KP
AD  - Battelle Memorial Institute, Columbus, OH 43201, USA.
FAU - Taylor, K L
AU  - Taylor KL
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, MD 20892-9825, USA.
FAU - Glaze, E
AU  - Glaze E
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, MD 20892-9825, USA.
FAU - VanRaden, M
AU  - VanRaden M
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, MD 20892-9825, USA.
FAU - Schiffer, J M
AU  - Schiffer JM
AD  - Centers for Disease Control and Prevention, Atlanta, GA 30329-4027, USA.
FAU - Hewitt, J A
AU  - Hewitt JA
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, MD 20892-9825, USA.
FAU - Quinn, C P
AU  - Quinn CP
AD  - Centers for Disease Control and Prevention, Atlanta, GA 30329-4027, USA.
FAU - Nuzum, E O
AU  - Nuzum EO
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, MD 20892-9825, USA.
LA  - eng
GR  - HHSN272201200003I/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20160504
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Anthrax Vaccines)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antibodies, Neutralizing)
RN  - Inhalation anthrax
SB  - IM
MH  - Animals
MH  - Anthrax/*prevention & control
MH  - Anthrax Vaccines/*administration & dosage/*immunology
MH  - Anti-Bacterial Agents/*therapeutic use
MH  - Antibodies, Bacterial/blood
MH  - Antibodies, Neutralizing/blood
MH  - Bacillus anthracis/*immunology
MH  - Female
MH  - Macaca fascicularis
MH  - Male
MH  - Post-Exposure Prophylaxis/*methods
MH  - Random Allocation
MH  - Respiratory Tract Infections/*prevention & control
MH  - Survival Analysis
MH  - Vaccination
PMC - PMC5097032
MID - NIHMS783283
OTO - NOTNLM
OT  - Anthrax
OT  - Bacillus anthracis
OT  - BioThrax
OT  - Correlates of protection
COIS- None to report.
EDAT- 2016/05/08 06:00
MHDA- 2017/12/16 06:00
PMCR- 2017/12/12
CRDT- 2016/05/08 06:00
PHST- 2015/12/17 00:00 [received]
PHST- 2016/04/08 00:00 [revised]
PHST- 2016/04/18 00:00 [accepted]
PHST- 2016/05/08 06:00 [pubmed]
PHST- 2017/12/16 06:00 [medline]
PHST- 2016/05/08 06:00 [entrez]
PHST- 2017/12/12 00:00 [pmc-release]
AID - S0264-410X(16)30202-X [pii]
AID - 10.1016/j.vaccine.2016.04.048 [doi]
PST - ppublish
SO  - Vaccine. 2016 Dec 12;34(51):6518-6528. doi: 10.1016/j.vaccine.2016.04.048. Epub 
      2016 May 4.