Evaluation and Characterization of Neutralizing Antibodies against Viruses Relevant to Blood-Derived Products

Principal Investigator: Pei Zhang, PhD
Office / Division / Lab: OBRR / DH / LPD

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Overview

Public Health Issue: Current assays for measuring anti-HCV antibody potency are not optimal. Developing reliable methods for measuring potency of HCV Immune Globulin is essential in the development of these products for use in preventing and/or treating HCV disease.

Regulatory Contribution: The potency of some specific immune globulins, such as immune globulins against HCV (HCVIGIV), is currently determined by using highly variable biological assays with a poor degree of specificity. Advances made in this area are essential for clinical trials supporting licensure of these products. The validity of clinical endpoints in these studies depends on accurate determination of the level of relevant antibodies in HCVIGIV, as well as an accurate assessment of titers of neutralizing antibody in study subjects.

Research Approach: Using a multidisciplinary approach involving techniques such as random peptide phage-display, kinetic capillary electrophoresis, bioinformatics, and in vitro neutralization assays, we characterize virus-specific neutralizing antibodies in HCVIGIV and patient sera, and identify their corresponding epitopes to establish neutralization epitope-based potency assays. The sensitivity, specificity, accuracy, linearity and robustness of these assays will be assessed according to FDA and ICH guidelines.

Mission Relevance & Outcomes: Development of neutralization epitope-based potency assays should facilitate the evaluation of FDA-regulated immune globulin products. Preparation and evaluation of any experimental IGIV (e.g. HCVIGIV), based on neutralization epitopes, will permit the development of a reference material for establishing parameters and standards critical to future product studies and improvements.

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Publications

Proc Natl Acad Sci U S A 2007 May 15;104(20):8449-54
Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma.
Zhang P, Wu CG, Mihalik K, Virata-Theimer ML, Yu MY, Alter HJ, Feinstone SM

Proc Natl Acad Sci U S A 2006 Jun 13;103(24):9214-9
Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees.
Zhang P, Yu MY, Venable R, Alter HJ, Shih JW

Proc Natl Acad Sci U S A. 2004 May 18;101(20):7705-10.
Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma.
Yu MY, Bartosch B, Zhang P, Guo ZP, Renzi PM, Shen LM, Granier C, Feinstone SM, Cosset FL, Purcell RH.