Studies on the Safety and Efficacy of Plasma-derived Products and their Recombinant Analogs

Principal Investigator: Basil Golding, MD
Office / Division / Lab: OBRR / DH / LPD

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Overview

Public Health Issue: Plasma-derived products are used to treat serious, life-threatening diseases such as Primary Immune Deficiency, coagulation and other protein deficiency disorders. Ensuring the safety of these products is an important public health issue.

Regulatory Contribution: Twenty five percent of infusions cause adverse reactions - this is probably due to the fact that fractionation involves non-sterile upstream steps. So although sterile filtration removes intact bacteria, contamination of the product with bacterial components is common and almost unavoidable. Detection of these contaminants at levels that will cause adverse events is important.

Research Approach: Toll-like receptors (TLRs) recognize bacteria, viruses and fungi. This system will be adapted to design a high-throughput assay to measure bacterial components in our products. Also, in vitro and in vivo models have been developed to assess animal-derived anti-anthrax antibodies.

Mission Relevance & Outcomes: We have developed cell lines that express human TLRs and shown that they can be used to detect bacterial components. These cell lines will be used to establish methods to detect microbial components in our products and thus improve their safety. Current methods employ non-human systems (rabbit pyrogen and LAL test) and mainly detect endotoxin but not other microbial components.

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Publications

Biologicals 2007 Oct;35(4):285-95
Development and evaluation of an ELISA for quantification of human alpha-1-proteinase inhibitor in complex biological mixtures.
Karnaukhova E, Golding B, Ophir Y

Biologicals 2007 Oct;35(4):285-95
Development and evaluation of an ELISA for quantification of human alpha-1-proteinase inhibitor in complex biological mixtures.
Karnaukhova E, Golding B, Ophir Y

Cancer Res 2007 May 15;67(10):5059
Regulatory B cells inhibit antitumor immunity.
Inoue S, Scott D, Golding B, Leitner WW

Microbes Infect 2007 Jan;9(1):55-62
Brucella abortus bacA mutant induces greater pro-inflammatory cytokines than the wild-type parent strain.
Parent MA, Goenka R, Murphy E, Levier K, Carreiro N, Golding B, Ferguson G, Roop RM 2nd, Walker GC, Baldwin CL

Vaccine 2006 Jul 26;24(31-32):5872-80
Passive immunotherapy of Bacillus anthracis pulmonary infection in mice with antisera produced by DNA immunization.
Herrmann JE, Wang S, Zhang C, Panchal RG, Bavari S, Lyons CR, Lovchik JA, Golding B, Shiloach J, Lu S

Amino Acids 2006 Jun;30(4):317-32
Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use.
Karnaukhova E, Ophir Y, Golding B

Immunol Lett 2005 Sep 15;100(2):195-201
The cytotoxic T lymphocyte response against a protein antigen does not decrease the antibody response to that antigen although antigen-pulsed B cells can be targets.
Wang W, Golding.

J Immunol 2005 Sep 15;175(6):3964-70
Th1-Like Cytokine Induction by Heat-Killed Brucella abortus Is Dependent on Triggering of TLR9.
Huang LY, Ishii KJ, Akira S, Aliberti J, Golding.

Thromb Res 2005;116(4):335-44
Identification of a novel immunodominant cytotoxic T lymphocyte epitope derived from human factor VIII in a murine model of hemophilia A.
Wang W, Merchlinsky M, Inman J, Golding.

Vaccine 2005 Feb 25;23(14):1730-8
Programming of CTL with heat-killed Brucella abortus and antigen allows soluble antigen alone to generate effective secondary CTL.
Inoue S, Golding B, Scott.

Clin Diagn Lab Immunol 2004 Nov;11(6):1158-64
Characterization of Antibodies to Capsular Polysaccharide Antigens of Haemophilus influenzae Type b and Streptococcus pneumoniae in Human Immune Globulin Intravenous Preparations.
Mikolajczyk MG, Concepcion NF, Wang T, Frazier D, Golding B, Frasch CE, Scott D.

J Med Primatol 2004 Aug;33(4):167-74
Systemic and mucosal immunity in rhesus macaques immunized with HIV-1 peptide and gp120 conjugated to Brucella abortus.
Eller N, Golding H, Inoue S, Beining P, Inman J, Matthews N, Scott DE, Golding B.