Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax

Nutan Mytle, Robert J. Hopkins, Nina V. Malkevich, Subhendu Basu, Gabriel T. Meister, Daniel C. Sanford, Jason Comer, Kristopher E. Van Zandt, Mohamed Al-Ibrahim, William G. Kramer, Cris Howard, Nancy Daczkowski, Ajoy C. Chakrabarti, Boris Ionin, Gary S. Nabors, Mario H. Skiadopoulos

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5684-5692
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume57
Issue number11
DOIs
StatePublished - Nov 1 2013
Externally publishedYes

Fingerprint

Primates
Toxemia
Bacillus anthracis
Anthrax
Rabbits
Spores
Antigens
Therapeutics
Anthrax Vaccines
Pharmacokinetics
Survival
Body Temperature
Intravenous Infusions
Inhalation
Half-Life
Inhalation anthrax
Anthrax Immune Globulin Intravenous
Immunoglobulins
Volunteers
Healthy Volunteers

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Mytle, N., Hopkins, R. J., Malkevich, N. V., Basu, S., Meister, G. T., Sanford, D. C., ... Skiadopoulos, M. H. (2013). Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax. Antimicrobial Agents and Chemotherapy, 57(11), 5684-5692. https://doi.org/10.1128/AAC.00458-13

Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax. / Mytle, Nutan; Hopkins, Robert J.; Malkevich, Nina V.; Basu, Subhendu; Meister, Gabriel T.; Sanford, Daniel C.; Comer, Jason; Van Zandt, Kristopher E.; Al-Ibrahim, Mohamed; Kramer, William G.; Howard, Cris; Daczkowski, Nancy; Chakrabarti, Ajoy C.; Ionin, Boris; Nabors, Gary S.; Skiadopoulos, Mario H.

In: Antimicrobial Agents and Chemotherapy, Vol. 57, No. 11, 01.11.2013, p. 5684-5692.

Research output: Contribution to journalArticle

Mytle, N, Hopkins, RJ, Malkevich, NV, Basu, S, Meister, GT, Sanford, DC, Comer, J, Van Zandt, KE, Al-Ibrahim, M, Kramer, WG, Howard, C, Daczkowski, N, Chakrabarti, AC, Ionin, B, Nabors, GS & Skiadopoulos, MH 2013, 'Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax', Antimicrobial Agents and Chemotherapy, vol. 57, no. 11, pp. 5684-5692. https://doi.org/10.1128/AAC.00458-13
Mytle N, Hopkins RJ, Malkevich NV, Basu S, Meister GT, Sanford DC et al. Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax. Antimicrobial Agents and Chemotherapy. 2013 Nov 1;57(11):5684-5692. https://doi.org/10.1128/AAC.00458-13
Mytle, Nutan ; Hopkins, Robert J. ; Malkevich, Nina V. ; Basu, Subhendu ; Meister, Gabriel T. ; Sanford, Daniel C. ; Comer, Jason ; Van Zandt, Kristopher E. ; Al-Ibrahim, Mohamed ; Kramer, William G. ; Howard, Cris ; Daczkowski, Nancy ; Chakrabarti, Ajoy C. ; Ionin, Boris ; Nabors, Gary S. ; Skiadopoulos, Mario H. / Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax. In: Antimicrobial Agents and Chemotherapy. 2013 ; Vol. 57, No. 11. pp. 5684-5692.
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