Human Antibody Therapeutics For Viral Disease (Current Topics in Microbiology and Immunology)

196 Pages·2007·1.14 MB·English

by  Scott K. Dessain

Current Topics in Microbiology and Immunology
Volume 317
Series Editors
Richard W. Compans
Emory University School of Medicine, Department of Microbiology and
Immunology, 3001 Rollins Research Center, Atlanta, GA 30322, USA
Max D. Cooper
Howard Hughes Medical Institute, 378 Wallace Tumor Institute, 1824 Sixth
Avenue South, Birmingham, AL 35294-3300, USA
Tasuku Honjo
Department of Medical Chemistry, Kyoto University, Faculty of Medicine,
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Hilary Koprowski
Thomas Jefferson University, Department of Microbiology and Immunology,
Biotechnology Foundation Laboratories, 1020 Locust Street, Suite M85 JAH,
Philadelphia, PA 19107-6799, USA
Fritz Melchers
Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstr. 50 –
70, 4056 Basel Switzerland
Michael B.A. Oldstone
Department of Neuropharmacology, Division of Virology, The Scripps Research
Institute, 10550 N. Torreye Pines Road, La Jolla, CA 92037, USA
Sjur Olsnes
Department of Biochemistry, Institute for Cancer Research, The Norwegian
Radium Hospital, Montebello 0310 Oslo, Norway
Peter K. Vogt
The Scripps Research Institute, Dept. of Molecular & Exp. Medicine, Division of
Oncovirology, 10550 N. Torreye Pines Rd. BCC-239, La Jolla, CA 92037, USA
Scott K. Dessain
Editor
Human Antibody
Therapeutics
for Viral Disease
Scott K. Dessain, MD, PhD
Cardeza Foundation for Hematologic Research
Kimmel Cancer Center
Thomas Jefferson University
Curtis Building 812
1015 Walnut St.
Philadelphia, PA 19107
USA
E-mail: [email protected]
Cover Illustration: Decoration of the E16 neutralizing monoclonal antibody on the West Nile virion. The
E16 structural epitope is mapped in magenta onto the cyro-electron microscopic reconstruction of the
West Nile virion. Domains I, II, and III of West Nile virus E protein are represented in red, yellow, and
blue, respectively.
ISBN 978-3-540-72144-4 e-ISBN 978-3-540-72146-8
Current Topics in Microbiology and Immunology ISSN 0070-217X
Library of Congress Catalog Number: 72-152360
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Preface
Editor’s Introduction
Although the utility of human antibodies as medical therapeutics for cancer and
immune diseases has been well-established, it is only beginning to be realized for
the treatment of viral infectious diseases. Polyclonal immunoglobulins have long
been used for some viral diseases, but they have limited potency and disease scope.
It should theoretically be possible to create monoclonal or oligoclonal antibody
preparations that capture the essential curative functions of the humoral immune
response to viral pathogens, yet only a single humanized monoclonal antibody (pav-
ilizumab) has been approved as a viral countermeasure. Reliable technologies for
creating human or humanized antibodies with defined viral antigen specificities are
well-established. Accordingly, current antibody development efforts are focused on
identifying and cloning the particular antibodies that contain the fundamental cura-
tive potency of the polyclonal humoral immune response.
The limited spectrum of available viral antibody therapeutics may be attributed,
in part, to the unique technical challenges that each virus presents with regard to its
life cycle, capacity for spontaneous mutation, and clinical manifestations. The
articles in this volume address these issues from different perspectives. For
instance, the clinical value of an antibody may depend on the genetic stability of
the epitope it recognizes, the prevalence of that epitope in the viral population, the
kinetics of the antibody/antigen interaction, the functional implications of epitope
binding, and the interactions between the antibody and the immune system, which
are often mediated by the Fc portion of the antibody. In some settings, a single
antibody may be sufficient, whereas in others a combination of 2 or more may be
preferred.
The articles in this volume have been selected to demonstrate the progress in the
development of human antibody therapeutics for viral disease. Keck et al. review
the nature of the immune response to the Hepatitis C virus (HCV) and the details of
viral neutralization by antibodies, providing a conceptual model for the clinical use
of HCV-specific antibodies. Huber et al. summarize the initial clinical e xperiences
v
vi Preface
with antibody therapeutics for Human Immunodeficiency Virus (HIV), which can be
targeted to either the HIV virion or to host cell proteins. A discussion of the breadth
immune strategies that is required to control human rabies is provided by Nagarajan
et al., with a particular focus on India and other developing countries in which rabies
is endemic. The development of pavilizumab for RSV prophylaxis is reviewed in
Wu et al., in addition to results of antibody optimization studies that provide surpris-
ing insights and have broad general implications for anti-viral antibody engineering.
Melhop and Diamond explicate the biology of West Nile Virus (WNV) as a general
model for flaviviruses, while using their cloned antibodies as a springboard to con-
sider the mechanisms of WNV neutralization. The volume concludes with a descrip-
tion of methods to clone human antibodies in their native configurations, which
access a class of antibodies that differ from those obtained by recombinant DNA or
transgenic mouse methods.
The articles in this volume are definitive and comprehensive reviews written by
thought leaders who have sought to define the principles of viral neutralization by
human antibodies. They explore and anticipate the obstacles and opportunities that
will be encountered as the power of human antibodies is harnessed to address the
vast, un-met need for effective anti-viral therapeutics.
Philadelphia, PA Scott Dessain
March 2007
Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Therapeutic Control of Hepatitis C Virus:
The Role of Neutralizing Monoclonal Antibodies. . . . . . . . . . . . . . . . . . . . . 1
Z.Y. Keck, K. Machida, M.M.C. Lai, J.K. Ball, A.H. Patel,
and S.K.H. Foung
Antibodies for HIV Treatment and Prevention:
Window of Opportunity? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
M. Huber, W.C. Olson, and A. Trkola
Human Monoclonal Antibody and Vaccine Approaches
to Prevent Human Rabies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
T. Nagarajan, Charles E. Rupprecht, Scott K. Dessain,
P.N. Rangarajan, D. Thiagarajan, and V.A. Srinivasan
Immunoprophylaxis of RSV Infection: Advancing
from RSV-IGIV to Palivizumab and Motavizumab. . . . . . . . . . . . . . . . . . . 103
H. Wu, D.S. Pfarr, G.A. Losonsky, and P.A. Kiener
The Molecular Basis of Antibody Protection Against
West Nile Virus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
E. Mehlhop and M.S. Diamond
Exploring the Native Human Antibody Repertoire
to Create Antiviral Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
S.K. Dessain, S.P. Adekar, and J.D. Berry
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
vii
Contributors
Adekar, S.P.
Cardeza Foundation for Hematologic Research, Kimmel Cancer Center, Thomas
Jefferson University, Curtis Building 812, 1015 Walnut St., Philadelphia,
PA 19107, USA, [email protected]
Ball, J.K.
Institute of Infection, Immunity and Inflammation, School of Molecular Medical
Sciences, The University of Nottingham, Queen’s Medical Centre, Nottingham
NG7 2UH, UK
Berry, J.D.
Monoclonal Antibody and Bioforensic Development Sections, National
Microbiology Laboratory, Public Health Agency of Canada (PHAC), 1015 Arlington
St., Winnipeg, Manitoba R3E 3R2, Canada
Dessain, S.K.
Cardeza Foundation for Hematologic Research, Kimmel Cancer Center, Thomas
Jefferson University, Curtis Building 812, 1015 Walnut St., Philadelphia,
PA 19107, USA, [email protected]
Diamond, M.S.
Departments of Medicine, Molecular Microbiology, Pathology & Immunology,
Washington University School of Medicine, 660 South Euclid Avenue, Box 8051,
St. Louis, MO 63110, USA, [email protected]
Foung, S.K.H.
Department of Pathology, Stanford Medical School Blood Center, 800 Welch
Road, Palo Alto, CA, 94304, USA, [email protected]
Huber, M.
Division of Infectious Diseases, University Hospital Zurich, Rämistrasse 100,
8091 Zurich, Switzerland
Keck, Z.Y.
Department of Pathology, Stanford Medical School Blood Center, Palo Alto, CA,
94304, USA
ix
x Contributors
Kiener, P.A.
MedImmune, Inc., One MedImmune Way, Gaithersburg, MD 20878, USA
Lai, M.M.C.
Department of Molecular Microbiology and Immunology, University of Southern
California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles,
CA 90033, USA
Losonsky, G.A.
MedImmune, Inc., One MedImmune Way, Gaithersburg, MD 20878, USA
Machida, K.
Department of Molecular Microbiology and Immunology, University of Southern
California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles,
CA 90033, USA
Mehlhop, E.
Departments of Medicine, Molecular Microbiology, Pathology & Immunology,
Washington University School of Medicine, 660 South Euclid Avenue, Box 8051,
St. Louis, MO 63110, USA
Nagarajan, T.
Indian Immunologicals Limited Gachibowli Post, Hyderabad, India,
[email protected]
Olson, W.C.
Progenics Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown,
NY, 10591 USA
Patel, A.H.
MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street,
Glasgow G11 5JR, UK
Pfarr, D.S.
MedImmune, Inc., One MedImmune Way, Gaithersburg, MD 20878, USA
Rangarajan, P.N.
Indian Institute of Science, Bangalore, India
Rupprecht, C.E.
Centers for Disease Control and Prevention, Atlanta, GA, USA
Srinivasan, V.A.
Indian Immunologicals Limited Gachibowli Post, Hyderabad, India,
[email protected]
Thiagarajan, D.
Indian Immunologicals Limited Gachibowli Post, Hyderabad, India
Contributors xi
Trkola, A.
Division of Infectious Diseases, University Hospital Zurich, Rämistrasse 100,
8091 Zurich, Switzerland, [email protected]
Wu, H.
MedImmune, Inc., One MedImmune Way, Gaithersburg, MD 20878, USA,
[email protected]