title: Evaluation of immunogenicity and efficacy of anthrax vaccine adsorbed for postexposure prophylaxis.
abstract: Antimicrobials administered postexposure can reduce the incidence or progression of anthrax disease, but they do not protect against the disease resulting from the germination of spores that may remain in the body after cessation of the antimicrobial regimen. Such additional protection may be achieved by postexposure vaccination; however, no anthrax vaccine is licensed for postexposure prophylaxis (PEP). In a rabbit PEP study, animals were subjected to lethal challenge with aerosolized Bacillus anthracis spores and then were treated with levofloxacin with or without concomitant intramuscular (i.m.) vaccination with anthrax vaccine adsorbed (AVA) (BioThrax; Emergent BioDefense Operations Lansing LLC, Lansing, MI), administered twice, 1 week apart. A significant increase in survival rates was observed among vaccinated animals compared to those treated with antibiotic alone. In preexposure prophylaxis studies in rabbits and nonhuman primates (NHPs), animals received two i.m. vaccinations 1 month apart and were challenged with aerosolized anthrax spores at day 70. Prechallenge toxin-neutralizing antibody (TNA) titers correlated with animal survival postchallenge and provided the means for deriving an antibody titer associated with a specific probability of survival in animals. In a clinical immunogenicity study, 82% of the subjects met or exceeded the prechallenge TNA value that was associated with a 70% probability of survival in rabbits and 88% probability of survival in NHPs, which was estimated based on the results of animal preexposure prophylaxis studies. The animal data provide initial information on protective antibody levels for anthrax, as well as support previous findings regarding the ability of AVA to provide added protection to B. anthracis-infected animals compared to antimicrobial treatment alone.
authors: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors: Boris
authors: B
authors: Ionin
authors: Robert J
authors: RJ
authors: Hopkins
authors: Brett
authors: B
authors: Pleune
authors: Gloria S
authors: GS
authors: Sivko
authors: Frances M
authors: FM
authors: Reid
authors: Kristin H
authors: KH
authors: Clement
authors: Thomas L
authors: TL
authors: Rudge
authors: Gregory V
authors: GV
authors: Stark
authors: Alison
authors: A
authors: Innes
authors: Suha
authors: S
authors: Sari
authors: Tina
authors: T
authors: Guina
authors: Cris
authors: C
authors: Howard
authors: Jeffrey
authors: J
authors: Smith
authors: M Lisa
authors: ML
authors: Swoboda
authors: Ekaterina
authors: E
authors: Vert-Wong
authors: Virginia
authors: V
authors: Johnson
authors: Gary S
authors: GS
authors: Nabors
authors: Mario H
authors: MH
authors: Skiadopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000992:Antitoxins / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D011817:Rabbits; D016019:Survival Analysis; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*; D055815:Young Adult
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000992:Antitoxins
references: Lab Invest. 2003 Aug;83(8):1201-9
references: 12920249
references: Arch Pathol Lab Med. 1998 Nov;122(11):982-92
references: 9822127
references: Vaccine. 2004 Jan 2;22(3-4):422-30
references: 14670324
references: Clin Vaccine Immunol. 2008 Jun;15(6):946-53
references: 18417668
references: Antimicrob Agents Chemother. 2006 Nov;50(11):3535-42
references: 17065619
references: J Hyg (Lond). 1956 Mar;54(1):28-36
references: 13319688
references: Vaccine. 2001 Sep 14;19(32):4768-73
references: 11535328
references: Curr Opin Virol. 2012 Jun;2(3):353-6
references: 22709520
references: J Infect Dis. 2009 Feb 1;199(3):336-41
references: 19099484
references: Infect Immun. 2001 May;69(5):2888-93
references: 11292703
references: J Immunol Methods. 2008 Apr 20;333(1-2):89-106
references: 18304568
references: Vaccine. 2001 Aug 14;19(31):4409-16
references: 11483266
references: JAMA. 2002 May 1;287(17):2236-52
references: 11980524
references: Vaccine. 2006 Mar 24;24(14):2530-6
references: 16417950
references: Toxicon. 2001 Nov;39(11):1747-55
references: 11595637
references: Clin Vaccine Immunol. 2012 Nov;19(11):1730-45
references: 22933399
references: Clin Vaccine Immunol. 2012 Aug;19(8):1158-64
references: 22695155
references: Nature. 2004 Aug 19;430(7002):843-4
references: 15318206
references: J Infect Dis. 1993 May;167(5):1239-43
references: 8486963
references: PLoS One. 2010 Nov 08;5(11):e13888
references: 21079738
references: Emerg Infect Dis. 2002 Oct;8(10):1103-10
references: 12396924
references: Am J Public Health Nations Health. 1962 Apr;52(4):632-45
references: 18017912
references: Sci Transl Med. 2012 Sep 12;4(151):151ra126
references: 22972844