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Genomics, Proteomics and Vaccines Editor Guido Grandi Chiron Vaccines, Siena, Italy Genomics, Proteomics and Vaccines Genomics, Proteomics and Vaccines Editor Guido Grandi Chiron Vaccines, Siena, Italy Copyright # 2004 John Wiley & Sons, Ltd. The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, England Telephone (+44) 1243 779777 E-mail (for orders and customer service enquiries): [email protected] Visit our Home Page on www.wileyeurope.com or www.wiley.com All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1T 4LP, UK, without the permission in writing of the Publisher. Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, England, or emailed to [email protected], or faxed to (+44) 1243 770620. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the Publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Other Wiley Editorial Offices John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA Jossey-Bass, 989 Market Street, San Francisco, CA 94103-1741, USA Wiley-VCH Verlag GmbH, Boschstrasse. 12, D-69469 Weinheim, Germany John Wiley & Sons Australia Ltd, 33 Park Road, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd, 2 Clementi Loop #02-01, Jin Xing Distripark, Singapore 129809 John Wiley & Sons (Canada) Ltd, 22 Worcester Road, Etobicoke, Ontario, Canada M9W 1L1 Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0 470 85616 5 Typeset in 1012 /1212 Times by Keytec Typesetting Ltd, Bridport, Dorset, UK Printed and bound in Great Britain by Antony Rowe, Ltd., Chippenham, Wilts This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production. Contents Preface xi List of contributors xix PART 1: INTRODUCTION 1 Vaccination: Past, Present and Future 3 Maria Lattanzi and Rino Rappuoli 1.1 1.2 1.3 1.4 1.5 2 Introduction Vaccination: the past Vaccination: the present Vaccination: the future Conclusion: the intangible value of vaccination References Bioinformatics, DNA Microarrays and Proteomics in Vaccine Discovery: Competing or Complementary Technologies? 3 4 6 12 14 15 23 Guido Grandi 2.1 2.2 2.3 2.4 2.5 Introduction From genome sequence to vaccine discovery A case study: the anti-meningococcus B vaccine Comparison of the three approaches Conclusions: a ‘nomics’ approach to vaccine discovery References Genomics, Proteomics and Vaccines edited by Guido Grandi # 2004 John Wiley & Sons, Ltd ISBN 0 470 85616 5 23 25 28 34 37 40 vi CONTENTS PART 2: TECHNOLOGIES 3 Genome Sequencing and Analysis 45 Hervé Tettelin and Tamara Feldblyum 3.1 3.2 3.3 3.4 4 Introduction Genome sequencing Genome analysis Conclusion References Understanding DNA Microarrays: Sources and Magnitudes of Variances in DNA Microarray Data Sets 45 46 60 65 65 75 She-pin Hung, Suman Sundaresh, Pierre F. Baldi and G. Wesley Hatfield 4.1 4.2 4.3 4.4 4.5 5 Introduction DNA array formats Data analysis methods Sources and magnitudes of noise in DNA microarray experiments Conclusions Acknowledgements References The Proteome, Anno Domini Two Zero Zero Three 75 76 79 84 97 100 100 103 Pier Giorgio Righetti, Mahmoud Hamdan, Frederic Reymond and Joël S. Rossier 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Introduction Some definitions What methods exist to tackle the proteome complexity? Quantitative proteomics Pre-fractionation in proteome analysis Multi-dimensional chromatography Protein chip arrays Imaging mass spectrometry Acknowledgements References 103 105 107 112 117 120 123 126 127 127 CONTENTS 6 Mass Spectrometry in Proteomics vii 135 Pierre-Alain Binz 6.1 6.2 6.3 6.4 7 Introduction MS technology Principle of protein identification based on MS data Proteomics workflows References High Throughput Cloning, Expression and Purification Technologies 135 136 147 155 155 171 Andreas Kreusch and Scott A. Lesley 7.1 7.2 7.3 7.4 7.5 7.6 Introduction Gene cloning Protein expression High-throughput protein purification Validation of the pipeline and outlook Conclusion References 171 172 174 175 178 179 180 PART 3: APPLICATIONS 8 Meningococcus B: from Genome to Vaccine 185 Davide Serruto, Rino Rappuoli and Mariagrazia Pizza 8.1 8.2 8.3 9 Meningococcus, a major cause of bacterial meningitis Group B meningococcus as an example of reverse vaccinology Conclusions References Vaccines Against Pathogenic Streptococci 185 190 200 201 205 John L. Telford, Immaculada Margarit y Ros, Domenico Maione, Vega Masignani, Hervé Tettelin, Giuliano Bensi and Guido Grandi 9.1 9.2 9.3 9.4 9.5 Introduction Comparative genomics of streptococci A vaccine against group B streptococcus A vaccine against group A streptococcus Conclusions References 205 206 208 215 218 219 viii 10 CONTENTS Identification of the ‘Antigenome’ – a Novel Tool for Design and Development of Subunit Vaccines Against Bacterial Pathogens 223 Eszter Nagy, Tamás Henics, Alexander von Gabain and Andreas Meinke 10.1 10.2 10.3 10.4 10.5 10.6 10.7 11 Introduction Small DNA insert libraries – a tool to cover a pathogen’s ‘antigenome’ Proper display platforms Selected human sera to provide imprints of pathogen encounters Cognate antibodies reveal the ‘antigenome’ of a pathogen How to retrieve from the ‘antigenome’ the candidate antigens for vaccine development Summary and discussion References Searching the Chlamydia Genomes for New Vaccine Candidates 223 227 230 231 234 235 237 239 245 Giulio Ratti, Oretta Finco and Guido Grandi 11.1 11.2 11.3 11.4 12 Old problems and new perspectives for chlamydial vaccines Post-genomic approaches Genomic screening results Concluding considerations References Proteomics and Anti-Chlamydia Vaccine Discovery 245 250 251 262 263 267 Gunna Christiansen, Svend Birkelund, Brian B. Vandahl and Allan C Shaw 12.1 12.2 12.3 12.4 13 Introduction Proteome analysis Proteomics as a complement for genomics Benefits that proteomics provide for vaccine development References 267 269 277 279 280 Proteome Analysis of Outer Membrane and Extracellular Proteins from Pseudomonas aeruginosa for Vaccine Discovery 285 Stuart J. Cordwell and Amanda S. Nouwens 13.1 Introduction 285 CONTENTS 13.2 13.3 13.4 13.5 Index Membrane proteins in P. aeruginosa Extracellular proteins in P. aeruginosa Immunogenic proteins and vaccine discovery Conclusions References ix 286 292 296 298 299 305 Preface I have always been fascinated and intrigued by the history of human cultures and civilizations and how they have emerged and disappeared since 11 000 B.C., the date corresponding to the beginning of village life and the start of what geologists term the Recent Era. In mathematical terms, the complex function describing how prosperity of a given society has varied with time is defined by several variables, often interlinked. These include the availability of domesticable plant and animal species (indispensable to trigger the passage from a hunter-gatherer to an agricultural lifestyle), climate, richness of the territory occupied and the appearance of individuals with strong personality and leadership. An additional important variable, which is often surprisingly neglected even in history textbooks, is human susceptibility to microbes and infectious diseases. Indeed, epidemics caused by a variety of human pathogens have often been associated with, if not responsible for, major changes in human history. The eminent bacteriologist Hans Zinsser once wrote: ‘Soldiers have rarely won wars. They more often mop up after the barrage of epidemics. And typhus with his brothers and sisters, – plague, cholera, typhoid, dysentery, – has decided more campaigns than Caesar, Hannibal, Napoleon, and the inspectors general of history’. There are several well documented examples supporting Zinsser’s position and highlighting how the fate of human populations has often been dictated by epidemics. In 430 B.C., Sparta and its Peloponnesian allies engaged in a bloody war against the Athenians, whose culture and power were at their height at that time. The Spartan invasion forced an uncounted number of villagers to find protection within Athens’ city walls. As the war’s great chronicler Thucydides wrote, the crowded city was soon scourged by a plague that killed a huge Genomics, Proteomics and Vaccines edited by Guido Grandi # 2004 John Wiley & Sons, Ltd ISBN 0 470 85616 5 xii PREFACE number of Athenians. The plague weakened Athens to such an extent that, despite its great naval power, it took more than thirty years to defeat Sparta, and the city never regained its political and cultural glory. The dissolution of the great Roman empire has always been attributed to the decadence of the pagan lifestyle that led people to indulge in the pleasures of life rather than to protect the empire’s borders from barbarian invasions. However, historians seldom highlight the fact that from the second century on, new diseases appeared in Europe with increasing frequency and devastation. The Oronius, Galen and Cyprian plagues (so called from the names of the chroniclers who described them), together with the accompanying famines, severely reduced the empire’s population and abated its morale. In 452 A.D., when the Huns, headed by their ferocious general Attila, reached the gates of Rome, instead of entering the city, they halted and fell back. The withdrawal has often been attributed to the persuasive power of Pope Leo I, but, in fact, a severe epidemic, most likely smallpox, was raging within Rome, whose population, after subsequent epidemics, was soon to be reduced to a few thousand people. The Western Empire (in the fourth century, the Roman Empire had split into the Western Empire with its capital in Rome and the Eastern Empire with its capital in Costantinople) finally crashed in 476 A.D. During the following century, the great eastern emperor Justinian was reconquering western territories. By 542 A.D., he had taken back much of North Africa, Sicily and part of Spain. However, in the middle of his glorious campaigns the first indisputably reported bubonic plague broke out, causing one of the worst population crashes in human history. The Byzantine historian Procopius described it as ‘a pestilence by which the whole human race came near to being annihilated’. When the bout of plague ended, 40 percent of the people in Constantinople had died. Plague returned frequently until 590 A.D. and localized outbreaks occurred for another 150 years, halving human populations in many parts of the world. The Western Empire was never conquered again. In the 14th century, Europe was experiencing a period of cultural growth and expansion. The population continued to grow; Crusades and trade routes put Europe in contact with the Middle East, Arabia and China, favouring increasing literacy and promoting what would have been later called Renaissance. This flourishing expansion was dramatically slowed down by the worst disaster in human history, the second bubonic plague pandemic, the Black Death. It was brought into Europe in the summer of 1347 by Genoese traders who contracted it in the Crimean city port of Kaffa when it was under siege by Janibeg, Khan of Tartars (the legend says that before withdrawing because plague had started killing the Tartars, Janibeg ordered plague-infected corpses to be catapulted into Kaffa, thus spreading the epidemic within the city walls). The disease PREFACE xiii rapidly reached all the main cities in Europe and it was estimated that up to one half of the people in Europe, North Africa and Asia perished during the long epidemics. All aspects of European life, from art to commerce, were severely affected and the post-plague labour shortage was one of the main reasons for European involvement in the slave trade. The conquest of the Americas is usually attributed to the braveness, and sometime ferocity, of the Spanish conquistadores and of the European immigrants who succeeded in defeating the aggressive native populations. However, when Cortés attacked with his 300 soldiers the Aztec capital Tenochtitlán, he found the city, originally inhabited by 300,000 people, slaughtered by smallpox brought in by one of his African slaves who was affected by a virus strain to which Cortés’ soldiers were immune. In his battle report, Cortés wrote, ‘A man could not set his foot down unless on the corpse of an Indian’. Less than fifty years after Cortés arrived in Mexico, of the original 30 million people, only 3 million survived, 18 million having been killed by smallpox alone. Similarly, 80% of the Inca population in Peru disappeared in the 200 years following the Spanish invasion. In North America, the natives suffered similar slaughter by pathogens brought into their territories by European invaders. As in Latin America, it was mainly smallpox and measles that kept killing Amerindians, reducing by about 90% the original population of 100 million. As a result, Europeans succeeded in imposing their languages, religions, political power and what the historian Alfred Crosby called ecological imperialism, whereby most of the original ecosystems were completely europeanized by imported plant and animal species. Until the middle of the last century, infectious diseases were the first cause of death in humans; they continued to influence human cultures and civilizations and favoured the expansion of stronger, more immune-protected populations at the expense of weaker, immune-susceptible ones. In the second half of the 20th century, two extraordinary revolutions occurred, which had no precedents in history in terms of prolongation and amelioration of human life: the large scale availability of antibacterial drugs and the practice of mass vaccination. For the first time, bacterial infections could be effectively defeated and deadly viral and bacterial diseases such as smallpox, polio, rabies, tetanus and diphtheria could be prevented. In the developed countries, where antibiotics and vaccines were discovered and readily available, mortality rates from infectious diseases rapidly declined and lost their first ranking in the cause-of-death list, being overtaken by cancer and cardiovascular diseases. Smallpox global vaccination eradicated this killer virus, which now exists in only a few, well-contained laboratories, and anti-polio and anti-measles vaccines are expected to have similar effects within the next few years.