title: Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax.
abstract: Bacillus anthracis toxins can be neutralized by antibodies against protective antigen (PA), a component of anthrax toxins. Anthrivig (human anthrax immunoglobulin), also known as AIGIV, derived from plasma of humans immunized with BioThrax (anthrax vaccine adsorbed), is under development for the treatment of toxemia following exposure to anthrax spores. The pharmacokinetics (PK) of AIGIV was assessed in naive animals and healthy human volunteers, and the efficacy of AIGIV was assessed in animals exposed via inhalation to aerosolized B. anthracis spores. In the clinical study, safety, tolerability, and PK were evaluated in three dose cohorts (3.5, 7.1, and 14.2 mg/kg of body weight of anti-PA IgG) with 30 volunteers per cohort. The elimination half-life of AIGIV in rabbits, nonhuman primates (NHPs), and humans following intravenous infusion was estimated to be approximately 4, 12, and 24 days, respectively, and dose proportionality was observed. In a time-based treatment study, AIGIV protected 89 to 100% of animals when administered 12 h postexposure; however, a lower survival rate of 39% was observed when animals were treated 24 h postexposure, underscoring the need for early intervention. In a separate set of studies, animals were treated on an individual basis upon detection of a clinical sign or biomarker of disease, namely, a significant increase in body temperature (SIBT) in rabbits and presence of PA in the serum of NHPs. In these trigger-based intervention studies, AIGIV induced up to 75% survival in rabbits depending on the dose and severity of toxemia at the time of treatment. In NHPs, up to 33% survival was observed in AIGIV-treated animals. (The clinical study has been registered at ClinicalTrials.gov under registration no. NCT00845650.).
authors: Emergent BioSolutions Inc., Gaithersburg, Maryland, USA.
authors: Nutan
authors: N
authors: Mytle
authors: Robert J
authors: RJ
authors: Hopkins
authors: Nina V
authors: NV
authors: Malkevich
authors: Subhendu
authors: S
authors: Basu
authors: Gabriel T
authors: GT
authors: Meister
authors: Daniel C
authors: DC
authors: Sanford
authors: Jason E
authors: JE
authors: Comer
authors: Kristopher E
authors: KE
authors: Van Zandt
authors: Mohamed
authors: M
authors: Al-Ibrahim
authors: William G
authors: WG
authors: Kramer
authors: Cris
authors: C
authors: Howard
authors: Nancy
authors: N
authors: Daczkowski
authors: Ajoy C
authors: AC
authors: Chakrabarti
authors: Boris
authors: B
authors: Ionin
authors: Gary S
authors: GS
authors: Nabors
authors: Mario H
authors: MH
authors: Skiadopoulos
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000907:Antibodies, Bacterial / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D001408:Bacillus anthracis / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000302:isolation & purification / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008252:Macaca fascicularis; D008297:Male; D011817:Rabbits; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D013171:Spores, Bacterial / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D016019:Survival Analysis; D013997:Time Factors; D014611:Vaccination
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D015415:Biomarkers; C493276:Biothrax; D016756:Immunoglobulins, Intravenous; C030325:anthrax toxin
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