Vaccinology E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1379

Veröffentlichungsjahr: 2012

Beschreibung

Covering all aspects of vaccine research and development in one volume, this authoritative resource takes a comprehensive and systematic approach to the science of vaccinology focusing not only on basic science, but also on the many stages required to commercialize and navigate the regulatory requirements for human application, both in the United States and Europe.

• Reviews in detail the process of designing a vaccine, from the initial stages of antigen discovery to human application
• Includes evaluation of vaccine efficacy and safety
• Details clinical trial design, including regulatory requirements
• Discusses the emerging field of active cellular immunotherapy

Vaccinology: Principles and Practice provides an invaluable resource for clinicians, scientific and medical researchers, lecturers and postdoctoral fellows working in the field of vaccines.

Leseprobe

Contents

Cover

Title Page

Copyright

List of Contributors

Preface

Part 1: Introduction

Chapter 1: Concept and Scope of Modern Vaccines

Introduction

Triumphs and limitations of current vaccination

Modern approaches that impact vaccine design

A return to attenuated organisms?

Improve existing vaccines and vaccine uptake

Hurdles and challenges for the future

Part 2: Principles of Vaccine Design

Chapter 2: Strategies to Stimulate Innate Immunity for Designing Effective Vaccine Adjuvants

Principles of vaccine design: stimulation of innate immunity

Innate immune stimulators

Practical applications for adjuvants

Summary

Acknowledgements

Chapter 3: Antigen Processing and Presentation by MHC Class I, II, and Nonclassical Molecules

MHC class I and II structure

MHC molecule assembly

Peptide generation

Cross- and criss-cross presentation

Summary

Acknowledgments

Chapter 4: Understanding the Mucosal Immune System for Better Mucosal Vaccine Design

Introduction

Anatomy of the mucosal immune system

Players of the mucosal immune system

Mucosal vaccines: current strategies and ongoing challenges

Final word

Chapter 5: Immunologic Memory: T Cells in Humans

Introduction

Generation of memory T cells

Induction of T-cell memory with a vaccine

Concluding remarks

Acknowledgments

Chapter 6: Immunologic Memory: B Cells

Introduction

Human evaluation of B-cell vaccine responses

Variability in antibody maintenance is dependent on the type of vaccine

Primary B-cell immune response

Secondary B-cell immune responses

Factors important for long-lived plasma cell generation

Heterogeneity of the circulating newly formed ASCs

Models of long-lived plasma cells maintenance

Heterogeneity of human memory B-cell subsets

Measuring memory B-cell responses to vaccines

Antibody maintenance is dependent on the age of the host

Location of memory B cells and plasma cells may play a role in protection

Biomarkers of long-lived humoral immunity during vaccine priming

Chapter 7: Utility of Mouse Models in Vaccine Design and Development

Why the Mouse?

Why mouse models for vaccine development

Experimental mouse models of human pathogens

Mice as models for lethal human pathogens

Concluding remarks

Chapter 8: Utility of Nonhuman Primate Models for Vaccines

Introduction

SIVs and SIV/HIV hybrid viruses (SHIV) used for vaccine studies

SIVmac group: SIVmac251, SIVmac239, and vaccine challenge viruses

SIVB670/H4/H9 group and vaccine challenge viruses

SHIV group

HIV-1 infection of pig-tailed macaques

Challenge routes of infection for testing vaccine efficacy

AIDS vaccine models

Acknowledgments

Part 3: Antigen Discovery

Chapter 9: Sequence-Based Computational Approaches to Vaccine Discovery and Design

Introduction

Designing vaccines based on alignments

Designing vaccines using epitope prediction

Conclusions

Chapter 10: Antigen Discovery for Vaccines Using High-throughput Proteomic Screening Technologies

Introduction

''Synthetic'' proteomes

HT antibody screening

T-cell screening platforms

Strategies for identification of protective antigens

Translation of HT screening into protective vaccines

Future challenges

Chapter 11: Phage Libraries

Introduction

Peptide mimotopes

Infectious disease mimotopes

Cancer mimotopes

Other mimotope applications

Phage vaccines

Antigen discovery and epitope mapping

Conclusion and future direction

Part 4: Antigen Engineering

Chapter 12: Attenuated Bacterial Vaccines

Introduction

Live attenuated, killed, or subunit vaccines?

Existing live attenuated vaccines

Rationally attenuated live vaccines

Auxotrophs

Regulatory mutants

Immune responses to live attenuated vaccines

Safety of live attenuated vaccines

Live attenuated vaccines as vaccine carriers

Conclusions

Chapter 13: Virus-like Particles as Antigen Scaffolds

Virus-like particles, a new class of vaccines

Properties of VLPs that promote immune responses

Commercial VLP-based vaccines

Exploiting VLPs as platform for antigenic display of heterologous target molecules

Recombinant VLPs

Display of target antigens by chemical conjugation

Recombinant virosomes

Synthetic multivalent platforms

Conclusions

Acknowledgments

Chapter 14: Recombinant MVA vaccines: Optimization, Preclinical, and Product Development

Aims of the chapter

Introduction to MVA

MVA molecular biology and replication

Construction and use of recombinant MVA

rMVA development

Summary

Acknowledgments

Chapter 15: Recombinant Adenoviruses for Vaccination

Adenovirus vectors for vaccination: advantages and problems

Basic concepts of Ad vaccination

Specific examples for Ad-based vaccination

Conclusions and future directions

Chapter 16: Recombinant Avipoxviruses

Introduction

Avipoxvirus phylogeny

Disease control: vaccination and transmission control

Recombinant vector strains

Biosafety and environmental safety

Genome sequences

Promoters

Insertion sites

Recombination strategies

Recombinant selection and screening

Propagation of rFWPV

Poultry vaccines

Mammalian vaccines: background and introduction

Mammalian vaccines: veterinary

Preclinical and clinical human vaccine trials

Immune responses induced by avipoxvirus vectors

Enhanced avipoxvirus vectors

Acknowledgments

Chapter 17: Intracellular Facultative Bacterial Vectors for Cancer Immunotherapy

Patho-biotechnology and the challenge of tumor immunotherapy

The biology of intracellular bacterial vectors

Bacille Calmette-Guérin

Shigella flexneri

Salmonella enterica

Listeria monocytogenes

Discussion

Chapter 18: Nucleic Acid Vaccination

Background

Modifications of genes and gene expression

Infectious diseases

Cancer

Allergy and autoimmune diseases

Licensed DNA vaccines

Delivery

Production

Chapter 19: Artificial Antigen-presenting Cells: Large Multivalent Immunogens

Introduction

CD8 T-cell activation and memory development

Activation of CD8 T cells for tumor immunotherapy

Artificial APC for ex vivo activation and adoptive transfer of T cells

Artificial APC for in vivo T-cell activation: large multivalent immunogen

Future directions

Acknowledgments

Part 5: Delivery Systems

Chapter 20: Transcutaneous Immunization via Vaccine Patch Delivery System

Introduction

Skin immunology system and TCI mechanism

General TCI principles learned from preclinical studies

Clinical studies involving TCI using early-stage, “wet” patch format

Technical advances: dry vaccine patch delivery system

Recent clinical applications with LT dry patches

Commentary and future direction

Acknowledgments

Chapter 21: Needle-free Jet Injection for Vaccine Administration

Introduction

Liquid jet injectors

Solid jet injectors

Conclusion

Chapter 22: Oral Vaccines: An Old Need and Some New Possibilities

Introduction

Polio vaccine

Cholera vaccine

Typhoid vaccine

Rotavirus vaccine

Plant-derived vaccines: current status and challenges ahead

Plant-based vaccine trials

Acknowledgments

Chapter 23: Adjuvants: From Serendipity to Rational Discovery

What are adjuvants and why do we need them?

Safety safety safety

Mechanisms of adjuvanticity: the target cells

Mechanisms of adjuvanticity: the target molecules

Outlook: what will the adjuvants of the future look like?

Conclusions

Chapter 24: Immunostimulatory Properties of Biodegradable Microparticles

Introduction

Particulate vaccine adjuvants

Combination vaccine adjuvants

How do particulate vaccine adjuvants work?

Chapter 25: Co-administration of Co-stimulatory Moieties

Introduction

Negative regulatory members of the CD28 superfamily

Negative regulatory pathways and enhancement of tumor immunity

Negative pathways and viral infections

Blocking positive co-stimulation signals in autoimmunity

Conclusion

Chapter 26: Toll Receptors in Relation to Adjuvant Effects

Toll-like receptors

TLR signaling

TLRs in immunity

TLR agonists as vaccine adjuvant

Safety issues and open questions

Future directions

Acknowledgments

Part 6: Regulatory Considerations

Chapter 27: Regulatory Issues (FDA and EMA)

Vaccines: an overview

DNA vaccines and monoclonal antibody vaccines

Herceptin®

Cervarix®

Provenge®

Yervoy™ (ipilimumab)

Swine flu vaccine

Use of transgenic animals in vaccine development

EU licensing system

US licensing system

Reforms within the EMA and FDA

Conclusion

Acknowledgment

Part 7: Evaluating Vaccine Efficacy

Chapter 28: Immune Monitoring Design within the Developmental Pipeline for an Immunotherapeutic or Preventive Vaccine

Introduction

Challenges for immune monitoring

Immune monitoring design along the vaccine pipeline

Sample logistics

Current established assays

Complex assays

New technologies

Qualification and validation of immune monitoring assays

Response definition

Summary

Chapter 29: Clinical Development Strategy: Nuts and Bolts

Introduction

Rotavirus

Human papillomavirus

Summary

Acknowledgment

Chapter 30: Current Approaches to Identify and Evaluate Cancer Biomarkers for Patient Stratification

General overview

Breast cancer: developmental risk

Molecular heterogeneity of breast cancer

Prediction of outcome based on clinicopathological features

Prediction of outcome based on molecular features and profiling

Prediction of response to therapy

Toward personalized medicine for breast cancer patients

Omic technologies

Patient modeling based on genomic and proteomic data

Perspective on biomarkers in personalized medicine

Acknowledgments

Part 8: Implementing Immunizations/Therapies

Chapter 31: Mass Immunization Strategies

Mass immunization: history and concept

Routine and mass immunization as complementary strategies

Preventing and responding to emerging outbreaks

Accelerated disease control

Mass immunization for disease eradication: example polio eradication

Mass immunization campaigns: programmatic issues

Mass immunization: future outlook

Chapter 32: The Role of Mathematical Models in Vaccine Development and Public Health Decision Making

Introduction

Key concepts of infectious disease spread and control

Cost-effectiveness analysis

The application of mathematical models at different stages of vaccine development

Discussion

Chapter 33: Vaccine Safety

Overview of post-licensure monitoring

Overview of methodology and systems used to study vaccine safety

Clinical vaccine safety research and practice

Case studies

Approach to vaccine safety controversies

Summary

Index

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List of Contributors

Murrium Ahmad, PhD

The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK

Sir Roy M. Anderson, FRS, FMedSci

Chair in Infectious Disease Epidemiology

Division of Epidemiology, Public Health and Primary Care, School of Public Health, London, UK

Antony N. Antoniou, PhD

Senior Research Fellow Department of Infection and Immunity/Centre of Rheumatology, University College London, London, UK

Victor Appay

INSERM UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie (UPMC), Sorbonne Universités, and Hôpital Pitié-Salpétrière, Paris, France

Carolina Arancibia-Cárcamo, PhD

Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

Helen S. Atkins, BSc, PhD

Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, UK

R. Bruce Aylward, MD, MPH

Assistant Director-General, Polio, Emergencies and Country Collaboration, World Health Organization, Geneva, Switzerland

Lorne A. Babiuk, OC, SOM, PhD, DSc, FRSC

Office of Vice President Research, University of Alberta, Edmonton, Canada

Graham Ball

The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, and CompanDX Ltd, Nottingham, UK

Janine Bilsborough, PhD

Inflammation Research, Amgen, Thousand Oaks, CA, USA

Marie-Claude Boily, PhD

Senior Lecturer in Infectious Disease Ecology

Division of Epidemiology, Public Health and Primary Care, School of Public Health, London, UK

Diane L. Bolton

Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA

Catharine M. Bosio, PhD

Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA

Marc Brisson, PhD

Unité de Recherche en Santé des Populations, Centre de Recherche Fonds de la Recherche en Santé du Québec du Centre Hospitalier affilié Universitaire de Québec, Canada

Victoria Byers

NJM European Economic & Management Consultants Ltd, Gosforth, Newcastle Upon Tyne, UK

Claudio Carini, MD, PhD

Boston Biotech Clinical Research, Cambridge, MA, USA

Miles W. Carroll, PhD

Microbiology Division, Health Protection Agency, Porton Down, UK

Darrick Carter, PhD

Protein Advances, Inc., Seattle, WA, and Infectious Disease Research Institute, Seattle, WA, USA

Bryce Chackerian, PhD

Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, USA

Dipshikha Chakravortty, PhD

Department of Microbiology and Cell Biology, Center for Infectious Disease Research and Biosafety Laboratories, Indian Institute of Science, Bangalore, India

Robert T. Chen, MD, MA 

Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA

Zhengrong Cui

Pharmaceutics Division, College of Pharmacy, University of Texas-Austin, Austin, USA

Julie M. Curtsinger, PhD

Department of Laboratory Medicine & Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN, USA

Priyanka Das

Department of Microbiology and Cell Biology, Center for Infectious Disease Research and Biosafety Laboratories, Indian Institute of Science, Bangalore, India

Nelson Cesar Di Paolo, PhD

Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA

Candida Fratazzi, MD

Boston Biotech Clinical Research, Cambridge, MA, USA

Volker Gerdts, DVM

Vaccine & Infectious Disease Organization, Saskatoon; Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada

Jane Gidudu MD, MPH

Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA

Gregory M. Glenn

Intercell USA, Inc., Gaithersburg, MD, USA

David B. Guiliano

Division of Infection and Immunity/Centre for Rheumatology, Windeyer Institute of Medical Science, University College London, London, UK

Patrick Guirnalda, PhD

Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA

Yper Hall, BSc

Microbiology Division, Health Protection Agency, Porton Down, UK

David L. Heymann, MD, DTM&H

Professor and Chair, Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK

Maria Candela Iglesias

INSERM UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie (UPMC), Sorbonne Universités, and Hôpital Pitié-Salpétrière, Paris, France

John Iskander, MD, MPH

Office of the Associate Director for Science, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA

Camilla Jandus, MD, PhD

Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland

Sylvia Janetzki, MD

Zellnet Consulting, Inc., Fort Lee, NJ, USA

Ross M. Kedl, PhD

Department of Immunology, University of Colorado Denver, Denver, CO, USA

Amit Lahiri

Department of Microbiology and Cell Biology, Center for Infectious Disease Research and Biosafety Laboratories, Indian Institute of Science, Bangalore, India

Stephen M. Laidlaw

Department of Virology, Imperial College London Faculty of Medicine, London, UK

Yvette Latchman, PhD

The Puget Sound Blood Center, Seattle, WA, USA

Ed C. Lavelle, PhD

Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland

Stephanie Laversin

The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK

F. Eun-Hyung Lee, MD

Emory University Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Atlanta, GA, USA

Izabela Lenart

Division of Infection and Immunity/Centre for Rheumatology, Windeyer Institute of Medical Science, University College London, London, UK

André Lieber, MD, PhD

Department of Medicine, Division of Medical Genetics, and Department of Pathology, University of Washington, Seattle, WA, USA

Margaret A. Liu, MD

ProTherImmune, Lafayette, CA, USA

Amit A. Lugade, PhD

Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA

Megan MacLeod, PhD

Integrated Department of Immunology, Howard Hughes Medical Institute, National Jewish Health, Denver, CO, USA

Philippa Marrack, PhD

Integrated Department of Immunology, Howard Hughes Medical Institute, National Jewish Health, Denver, CO, USA

Preston A. Marx Jr, PhD

Tulane National Primate Research Center, Tulane University, Covington, LA, USA

Matthew F. Mescher, PhD

Department of Laboratory Medicine & Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN, USA

Benoit Mâsse, PhD

Public Health Sciences Division, Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Arnaud Moris

INSERM UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie (UPMC), Sorbonne Universités, and Hôpital Pitié-Salpétrière, Paris, France

Cliff Murray, PhD

Source BioScience, Nottingham, UK

George K. Mutwiri, DVM, PhD

Vaccine & Infectious Disease Organization, Saskatoon; School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada

Scott Napper, PhD

Vaccine & Infectious Disease Organization, Saskatoon; Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada

Derek T. O’Hagan, PhD

Global Head, Vaccine Delivery and Formulation, Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA

Yvonne Paterson, PhD

Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA

Andrew A. Potter, PhD, FCAHS

Vaccine & Infectious Disease Organization, Saskatoon; Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada

Simon J. Powis, PhD

School of Medicine, University of St Andrews, St Andrews, Fife, UK

Robert Rees

The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, and CompandX Ltd, Nottingham, UK

Mario Roederer, PhD

Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA

Pedro Romero

Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland

Iñaki Sanz, MD

Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA

Aaron K. Sato, PhD

OncoMed Pharmaceuticals, Redwood City, CA, USA

John T. Schiller, PhD

Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD, USA

Matthew Seavey, PhD

Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA

Robert C. Seid Jr

Intercell USA, Inc., Gaithersburg, MD, USA

Fiona A. Sharp, PhD

Fahmy Research Group, Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT, USA

Dmitry Shayakhmetov, PhD

Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA

Michael A. Skinner

Department of Virology, Imperial College London Faculty of Medicine, London, UK

Brian R. Sloat

Pharmaceutics Division, College of Pharmacy, University of Texas-Austin, Austin, USA

Kalathil Suresh, PhD

Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA

Rudolf H. Tangermann, MD

Global Polio Eradication Initiative, World Health Organization, Geneva, Switzerland

Yasmin Thanavala, PhD

Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA

Richard W. Titball, BSc, PhD, DSc, FRCPath

School of Biosciences, University of Exeter, Exeter, UK

Hugh Townsend, DVM, MSc

Vaccine & Infectious Disease Organization, Saskatoon; Department of Large Animal Clinical Sciences, University of Saskatchewan, Saskatoon, SK, Canada

Hoi K. Tran

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA

Sylvia van Drunen Littel-van den Hurk, PhD

Vaccine & Infectious Disease Organization, Saskatoon; Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada

Claudia Vellozzi, MD, MPH

Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA

Joanne L. Viney, PhD

Inflammation Research, Amgen, Thousand Oaks, CA, USA

Alexander F. Voevodin, MD, PhD, DSc, FRCPath

Vir&Gen, Toronto, ON, Canada

Andreas Wack

Division of Immunoregulation, National Institute for Medical Research, London, UK

Britta Wahren, MD, PhD

Department of Virology, Karolinska Institutet and Swedish Institute for Infectious Disease Control, Stockholm, Sweden

Heather L. Wilson, PhD

Vaccine & Infectious Disease Organization, Saskatoon; Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada

Peter Wilson, PhD, MBA, LLB

NJM European Economic & Management Consultants Ltd, Gosforth, Newcastle Upon Tyne, UK

Laurence Wood, PhD

Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA

Preface

“Vaccinology” is a term that encompasses the whole process of producing vaccines – from basic research and preclinical demonstration of efficacy, to approval and clinical trial in humans. While there are many excellent books that detail the various steps, such as antigen discovery or delivery systems, there are fewer that also cover so called “downstream development,” such as the design of clinical trials, or their regulation in the United States and the European Union. In this book we have aimed to fill this gap by providing the reader with a comprehensive and authoritative reference that describes the design and construction of vaccines from first principles to implementation. We hope it will appeal both to scientists engaged in vaccine research and development, and to clinicians, or indeed anyone, with an interest in the opportunities and challenges facing the development of new vaccines.

To tackle this vast subject we have organized the chapters into sections. We start with an examination of the concept and scope of modern vaccines. We follow this with the basic tenets of the immune system that govern our thinking about vaccines, with chapters on innate immunity, antigen processing and presentation, mucosal immunity, immunological memory in T and B cells, and the utility of mouse and nonhuman primate models for testing vaccine efficacy. In the following section we explore antigen discovery in the postgenomic era, during which there has been remarkable progress in proteomic mining for potential vaccine antigens, and powerful predictive algorithms and high-throughput assay and display technologies. Together these offer unprecedented opportunities for the rapid development of new vaccines. This is then followed by a selection of chapters on antigen engineering and delivery: attenuated microbe vaccines, virus-like particles, recombinant viruses (orthopox, avipox, lentivirus, and adenovirus) and bacteria, DNA vaccines, and artificial cells. In parallel we explore methods for antigen delivery, with chapters on transcutaneous vaccination, needle-free jet delivery, and oral vaccines. The need to potentiate otherwise inert proteins is the subject of the next section, with chapters on designing adjuvants, particulate delivery systems such as PLGs and microspheres, co-administration of co-stimulatory moieties, and the role of TLR signaling in adjuvanticity. We then transition from basic research to vaccine implementation. The first of these sections discusses regulatory considerations, with chapters on working with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), developmental pipelines, the design of clinical trials, immune monitoring and biomarkers, and vaccine safety. This is followed by chapters on mass immunization strategies, and mathematical models and epidemiological monitoring.

This book would not be possible without the impressive array of experts who have contributed chapters. We wish to thank every one of you for making this possible and bearing with us on this ambitious project. Finally we wish to thank the production team at John Wiley, especially Julie Elliott, Maria Khan, and Michael Bevan. This has been a team effort, but ultimately any omissions or errors are the responsibility of the editors. We welcome comments and feedback for future editions of this book.

W. John W. MorrowNadeem A. SheikhClint S. SchmidtD. Huw Davies

PART 1

Introduction

CHAPTER 1

Concept and Scope of Modern Vaccines

D. Huw Davies1, Clint S. Schmidt2, & Nadeem A. Sheikh3

1School of Medicine, University of California at Irvine, Irvine CA, USA 2NovaDigm Therapeutics, Inc., Grand Forks, ND, USA 3Clinical Immunology, Research, Dendreon Corporation, Seattle, WA, USA

Introduction

Historically, vaccination has probably had the greatest impact on human health of any medical intervention technique. Immunization is the only cost effective solution that can arrest and even eradicate infectious diseases. The science of vaccinology can be traced to the ancient Chinese, who protected against smallpox by the process of variolation, in which small quantities of scabs from a lesion of an infected person were intranasally inoculated [1]. This process was revived in the early 18th century when Lady Mary Montagu, who had observed variolation being practiced in Turkey, advocated its use to prevent smallpox. Modern vaccinology started as a proper scientific endeavor by Edward Jenner's findings that cowpox pustules would prevent smallpox infection [2]. His work was the first to be evaluated scientifically and established the scientific basis for using a related but less dangerous pathogen to engender immune responses that are cross-protective against the more virulent pathogen [3]. The seminal work and findings of Jenner lay unexploited for nearly a century until Louis Pasteur demonstrated that chickens could be protected from cholera by inoculation with attenuated bacteria [4]. Similar experiments also showed that sheep could be protected from anthrax [5]. This concept of weakening a pathogen to invoke the immune system to produce a response forms the basis of immunity elicited by the Bacille Calmette-Guérin (BCG) tuberculosis vaccine, first administered in 1921 [6] and still in wide use today.

Vaccines are defined as immunogenic preparations of a pathogen that evoke an immune response without causing disease. While attenuation and inactivation of pathogens are conventional approaches, and are still used, modern vaccines also exploit recent developments in immunology, genomics, bioinformatics, and structural and protein chemistry. At the heart of all vaccines is antigen – the ligand of the receptors of T and B lymphocytes. Lymphocytes are the effector cells of the adaptive immune system that mediate immunologic memory responses – the very hallmark of vaccination – which set vaccination apart from other forms of modern immune system manipulation, such as broad-spectrum immunopotentiators, cytokine therapy, or passive transfer of specific hyperimmune globulins derived from human plasma.