Absence of immunopathology associated with repeated IV administration of bovine Hb-based oxygen carrier in dogs

Robert G Hamilton, Nancy Kelly, Maria S. Gawryl, Virginia T. Rentko

Research output: Contribution to journalArticle

Abstract

BACKGROUND: A Hb-based oxygen carrier, HBOC-301, is licensed by the FDA for use as a single-dose product to treat anemia in canines. The objective of this study was to investigate the immunopathologic consequences of multiple doses of HBOC-301. STUDY DESIGN AND METHODS: HBOC-301 was administered intravenously at 1.3 g per kg (10 mL/kg) nine times over 50 weeks to each of eight splenectomized beagles. During interim weeks, HBOC-301-specific IgG antibody was quantified in serum by immunoassay. Immunofluorescence studies were performed on thin sections of control and test dog livers and kidneys to detect any IgG, IgM, IgA, or C3 deposition. Physiology (p50) studies evaluated the capacity of circulating HBOC-301-specific IgG antibody to competitively block the binding of oxygen to HBOC-301. RESULTS: HBOC-301-specific IgG antibody was detected in seven of eight HBOC-301-treated dogs by Week 6. Peak antibody levels occurred by Week 10 (after the third dose). Immunofluorescence studies detected comparable IgG, IgA, IgM, or C3 deposition patterns in the kidneys and livers of both control and test dogs, which indicated no selective antibody-mediated deposition from multiple HBOC-301 administrations. Moreover, HBOC-301-specific IgG antibody in serum was unable to inhibit oxygen binding to the HBOC-301 in vitro, which indicated that circulating antibody did not diminish the oxygen-binding capacity of HBOC-301. CONCLUSION: The immunologic, histologic, and physiologic data support the safety of multidose administration of HBOC-301 in canines.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalTransfusion
Volume41
Issue number2
DOIs
Publication statusPublished - 2001

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ASJC Scopus subject areas

  • Hematology
  • Immunology

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