Table Of ContentNOVEL STRATEGIES IN
THE DESIGN AND
PRODUCTION OF VACCINES
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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NOVEL STRATEGIES IN THE DESIGN AND PRODUCTION OF VACCINES
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NOVEL STRATEGIES IN
THE DESIGN AND
PRODUCTION OF VACCINES
Edited by
Sara Cohen and Avigdor Shafferman
Israel Institute for Biological Research
Ness-Ziona, Israel
Springer Science+Business Media, LLC
Library of Congress Cataloging-in-Publication Data
On file
Proceedings of the 39th OHOLO Conference on Vaccines: Novel Strategies in Design and Production,
held May 7-11,1995, in Eilat, Israel
ISBN 978-1-4899-1384-5 ISBN 978-1-4899-1382-1 (eBook)
DOI 10.1007/978-1-4899-1382-1
© 1996 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1996
Softcover reprint of the hardcover 1st edition 1996
1098765432 1
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written
permission from the Publisher
39TH OHOLO CONFERENCE
Eliat, Israel, May 7-11, 1995
SCIENTIFIC ORGANIZING COMMITTEE
Avigdor Shaffennan Israel Institute for Biological Research, Ness-Ziona, Israel
Sara Cohen Israel Institute for Biological Research, Ness-Ziona, Israel
MosheWhite Israel Institute for Biological Research, Ness-Ziona, Israel
Shaul Reuveny Israel Institute for Biological Research, Ness-Ziona, Israel
Baruch Velan Israel Institute for Biological Research, Ness-Ziona, Israel
SCIENTIFIC ADVISORY COMMITTEE
Ruth Arnon Weizmann Institute, Rehovot, Israel
Jonathan Gershoni Tel-Aviv University, Tel-Aviv, Israel
Rino Rappuoli IRIS, Siena, Italy
Amos Panet B.T.G., Jerusalem, Israel
Jerald Sadoff WRAIR, Washington D.C., United States
Florian SchOdel Insenn, Lyon, France
Raymond Spier Surrey University, Guildford, United Kingdom
v
ALEXANDER KOHN
1919-1994
The tradition of the OHOLO Conferences was initiated 39 years ago in 1955 in Oholo
on the banks of the Lake of Galilee. The aim of these was to bring together scientists from
abroad and from Israel and set the grounds for ongoing scientific interactions. The founder
and the driving force behind the OHOLO Conference was Professor Alexander Kohn, known
to everybody by his nickname Leshek. By finding the right balance between serious scientific
discussions and a very friendly atmosphere, Leshek established the specific character of the
OHOLO meetings. Leshek was famous for his generous hospitality. He spared no effort in
providing a warm welcome to the guests, from tours of historic sites to entertainment in the
evening, the epitome of which were his productions, depicting the topic of the specific
conference in a humoristic way. He pursued this task until his retirement from the Israel
Institute for Biological Research, HBR Ness Ziona in 1984.
Professor Alexander Kohn was born on March 8, 1919, in Poland. At the age of 18
he emigrated to Israel where he studied microbiology at the Hebrew University in Jerusalem
from 1937-1940. Being aware ofthe fate of the Jewish people during the Second World War,
he joined the Jewish Brigade (8th Army) and fought in North Africa and Italy through 1946.
After an absence of 6 years, he resumed his studies in the Hebrew University, and received
his M.Sc. degree in bacteriology in 1947. His Ph.D. thesis, dealing with the behavior of
microorganisms in the air under normal and artificial conditions, was awarded to him in
1952.
Leshek joined IIBR in 1952 and very soon became one of the leading faculty members
of the institute. In 1956 he was appointed Head of the Department of Biophysics, in 1960 he
became Deputy Director for Research, and in 1970 he was appointed the position of Director
of IIBR. His activity at IIBR was interspersed with sabbatical leaves at the Institute of
Microbiology, Rutgers University, where he collaborated with Prof. W. Szybalski, at the
Molecular Biology and Virus Laboratory, University of California at Berkeley, at the Imperial
Cancer Research Foundation, London, and at the Virus Oncology Laboratory, University of
Chicago.
vii
viii Dedication
Prof. Kohn acted as Vice President of the Israel Association for the Advancement of
Science, as well as president of the Israel Society for Microbiology, and served as member
of the editorial boards of the Israf!l Journal of Medical Science, the Journal of Medical
Virology, and Gene. He was appointed as Professor for Microbiology at the Tel-Aviv
University, Medical School and later acted as senate member.
Prof. Kohn's main research activity revolved around viruses and development of viral
vaccines, for human and veterinary diseases. In addition, he was fascinated by the process
of virus-cell interactions (budding), which eventually led him to numerous studies of
membrane structure and function. During the last period of his life, he applied his vast
knowledge of viral diseases to development of methods for rapid viral diagnostics.
Prof. Kohn's scientific publications totaled more than two hundred papers in re
viewed journals and meetings. He was an editor and author of six books. His two last books
are connected with moral issues related to research. False Prophets deals with fraud and
error in science and medicine, and Fortune and Failure deals with missed opportunities and
chance discoveries in science. Humor played a central part in Prof. Kohn's life. He was the
founder and editor oft he Journal ofI rreproducible Research (J.I.R.), a satirical journal where
scientists laugh at science and themselves.
Leshek died on November 29, 1994, after a short illness. His wife Chana, his son
Yoram and his daughter Ruth, and four grandchildren at his bedside.
PREFACE
Vaccination is one of the most efficient and cost effective methods of promoting
human health and has been in clinical use for at least 200 years. Nevertheless, infectious
diseases continue to constitute a constant threat to the well being of humanity. Common
pathogens, once believed to be under control, acquire increased virulence and resistance to
drugs, while exotic microorganisms emerged from hidden reservoirs to cause yet incurable
diseases in humans. These changes, together with epidemic outbreaks related to political and
socio-economic instabilities, increase the needs for the development of new, advanced
vaccines. In this volume, devoted to the proceedings of the 39th OHOLO Conference, we
present some of the recent strategies for the design and production of novel vaccines.
The advent of recombinant DNA technology has stimulated the production of several
subunit vaccines. In spite of the obvious advantages to this approach, the limited immuno
genicity of many subunit candidates has hindered their development. Strategies to enhance
the immunogenicity of subunit vaccines is therefore critical. Several approaches toward this
goal, including design of novel adjuvants and delivery systems as well as design of
advantageous carriers, are presented here. Among the carriers evaluated here are polypep
tides (flagellin, HBV core antigen, J3-galactosidase), attenuated virions (Vaccinia, Sindbis),
and nonpathogenic licensed bacteria (Salmonella).
The developments in molecular biology have also provided the tools for design of a
new generation of live vaccines. Live attenuated vaccines and native detoxified toxins,
derived in the past by empirical methods, can now be engineered by precise molecular
tailoring to offer a greater level of safety. This approach is exemplified in this volume by the
generation of genetically modified pertusis and cholera toxin vaccines, hybrid SFVI Sindbis
alphavirus, and attenuated bacterial vaccines for anthrax and cholera.
An additional development in the field of bacterial vaccines is related to the recent
large-scale application of subcellular fractions as demonstrated here for staphylcocci poly
saccharide vaccine and meningococcal outer membrane protein. This was brought about by
improving immunogenicity of these fractions by appropriate formulation.
The recent most revolutionary development in vaccination is related to nucleic acid
vaccines. Such vaccines are of particular interest not only for novelty of the concept but also
for practical advantages, as well as their capacity to generate both cellular and humoral
responses. The power of this approach is exhibited in this volume by evaluation of DNA
based vaccines to influenza, HIV and Mycobacterium tuberculosis.
The development of novel vaccines relies very much on the availability of effective
procedures for their production and evaluation in humans. Advances in vaccine production
in recent years include development of well characterized, validated manufacturing proc
esses with appropriate in-process controls as exemplified here in production of hepatitis and
influenza vaccines and formulation of various combination vaccines. Determination of
ix
x Preface
efficacy in preclinical and specifically in clinical trials is the ultimate step in vaccine
development. The complexity of such evaluation is demonstrated for HN, and an example
for efficacy assessment in humans under field conditions is presented for a live Shigella
vaccme.
These proceedings cannot, obviously, encompass all the advances made in vaccine
development during the recent years. Nevertheless, the directions and strategies presented
here offer reasons for hope that many novel vaccines for prevention, control, and possibly
eradication of diseases will be available for use in the near future.
We are obliged to all the contributors to this volume and to our colleagues: Ruth
Arnon, Jonathan Gershoni, Amos Panet, Rino Rappuoli, Shaul Reuveny, Jerald Sadoff,
Florian SchOdel, Raymond Spier, Baruch Velan, and Moshe White.
