The Vaccine Book

by Bloom; Bloom; Lambert

• ISBN13: 9780121072582
• ISBN10: 0121072584
• Edition: 1st
• Format: Paperback
• Copyright: 11/25/2002
• Publisher: Elsevier Science

Summary

The Vaccine Book provides comprehensive information on the current and future world of vaccines. It reveals the scientific opportunities and potential impact of vaccines, including economic and ethical challenges, problems encountered when producing vaccines, how clinical vaccine trials are designed, and how to introduce vaccines into widespread use. Although vaccines are now available for many diseases, there are still challenges ahead for major diseases such as AIDS, tuberculosis, and malaria. The Vaccine Book is designed for students, researchers, public health officials, and all others interested in increasing their understanding of vaccines. Topics unique to this book: * Ethics * Economics * Diseases that could be prevented * Clinical trial designs * Ideas about the future of vaccines * Challenges facing research scientists in the vaccine area * Burden of vaccine-preventable illness and the impact of vaccines * Scientific obstacles to be overcome by existing and new vaccines * Basic mechanisms of host immunity and pathogen interaction with host tissues * New approaches to future vaccines against challenging diseases * Real and perceived safety issues which dominate vaccine development and vaccination policies * Microbial pathogenesis as a basis for vaccine design * Planning vaccine trials * Introducing new vaccines into the healthcare system * Future challenges for vaccines and immunizations

Table of Contents

Contributors	xxiii
Preface	xxvii
Acknowledgments	xxix
1 GLOBAL BURDEN OF DISEASE
The Burden of Vaccine-Preventable Diseases
Maureen Birmingham
Claudia Stein
Introduction. The Global Burden of Infectious and Parasitic Diseases	1	(2)
Brief Historical Perspective of Vaccinology	3	(1)
The Smallpox Eradication Era	4	(1)
Establishment of the Expanded Program on Immunization (EPI)	4	(3)
Era of Accelerated Disease Control	7	(6)
Polio Eradication	7	(1)
Measles Control and Elimination	8	(2)
Tetanus	10	(1)
Diphtheria	11	(1)
Pertussis	12	(1)
New Era of Challenges and Opportunities in Vaccinology	13	(1)
The Quest for Vaccines against the ``Big Three''	14	(2)
HIV--AIDS	15	(1)
Malaria	15	(1)
Tuberculosis	16	(1)
Summary	16	(1)
Conclusion	16	(7)
References	17	(6)
Cost Effectiveness of Immunization: Asking the Right Questions
Ruth E. Levine
Introduction	23	(1)
Cost-Effectiveness Analysis (CEA) Defined	24	(1)
The Family of Economic Evaluation Methods	25	(1)
Is Immunization Cost-Effective?	26	(2)
What Do CEA Results Really Mean and for What Are They Useful?	28	(4)
Current Questions Requiring CEA	32	(2)
How Can Cost-Effectiveness Analysis Be Used to Inform Decisions about Increasing Immunization Coverage?	32	(1)
What Does CEA Tell Us about Whether and How to Introduce New Vaccines, Such as Hib and Hep B?	33	(1)
Should Decisions about Funding Eradication Campaigns Be Made on the Basis of CEA?	33	(1)
What Remains for Cost-Effectiveness Analysis?	34	(1)
Conclusion	35	(2)
References	35	(2)
Potential and Existing Impact of Vaccines on Disease Epidemiology
Elizabeth Miller
Introduction	37	(1)
Potential Epidemiological Outcomes	38	(1)
Containment	38	(1)
Elimination	38	(1)
Eradication	38	(1)
Surveillance of Immunization Programs	39	(1)
Immunization Policy Determination	39	(1)
Biological Determinants of Immunization Programs	40	(2)
Development of Mathematical Models	42	(4)
Model Structure	42	(1)
Flows between Compartments	43	(1)
Parameter Estimation	44	(1)
Reproduction Number	45	(1)
Model Validation	45	(1)
Examples of the Use of Mathematical Models to Guide Immunization Policy	46	(2)
Measles	46	(1)
Rubella	47	(1)
Varicella	48	(1)
Conclusion	48	(3)
References	49	(2)
2 IMMUNOLOGY
Basic Immunology of Vaccine Development
Robert A. Seder
John R. Mascola
Introduction	51	(1)
Overview of the Immune Response	52	(14)
Innate and Adaptive Immunity	52	(1)
Adaptive Cellular Immunity	53	(6)
CD4+ T-Cell Responses
CD8+ T-Cell Responses
Cellular Memory
Humoral Immunity	59	(7)
Antibodies
Cells and Antibody Production
T-Cell-Independent Antigens and Conjugate Vaccines
Isotype Switching and Affinity Maturation
B-Cell Memory
Mechanisms of Antibody-Mediated Protection
Immune Adjuvants
Determinants of Vaccine Protection	66	(7)
Prevention of Infection versus Prevention of Disease	66	(1)
Factors That Determine Vaccine Efficacy: Threshold, Time, and Place	66	(1)
Immune Responses Elicited by Various Vaccine Formulations: Newer Approaches for Developing Vaccines for Diseases Requiring Cellular Immunity	67	(1)
References	68	(5)
Immunological Requirements for Vaccines to Be Used in Early Life
Claire-Anne Siegrist
Introduction	73	(1)
Early Life Vaccine Antibody Responses	73	(3)
Antibody Responses to Current Infant Vaccines	73	(2)
May Neonatal Immunization Induce Tolerance Rather Than Immunity?	75	(1)
Meeting the Challenge of Improving Early Life Antibody Responses	75	(1)
Early Life T-Cell Responses	76	(2)
Characteristics of Early Life T-Cell Responses	76	(1)
Factors That Limit Early Life T-Cell Responses	77	(1)
Can Early Life Immunization Induce Adult-like CD4+ and CD8+ Vaccine Responses?	77	(1)
Influence of Maternal Antibodies on Infant Vaccine Responses	78	(2)
Determinants of Maternal Antibody Inhibition of Infant Vaccine Responses	78	(1)
Influence of Maternal Antibodies on Infant B- and T-Cell Responses	79	(1)
Can Novel Vaccines Circumvent the Inhibition of Maternal Antibodies?	79	(1)
Conclusion and Perspectives	80	(5)
References	81	(4)
3 TRIAL DESIGN FOR VACCINES
Clinical Development of New Vaccines: Phase 1 and 2 Trials
W. Ripley Ballou
Introduction	85	(2)
Phase 1: A Primary Focus on Safety	87	(1)
Practical Considerations for Phase 1 Studies	88	(2)
Proceeding to Phase 2	90	(2)
Conclusions	92	(3)
References	92	(3)
Phase 3 Studies of Vaccines
John D. Clemens
Hye-Won Koo
Introduction	95	(1)
Prelicensure Phasing of Vaccine Evaluations	95	(1)
Phase 3 Paradigm: The Randomized, Controlled Clinical Trial	96	(4)
Design	96	(2)
Strengths of the RCT Design in Phase 3 Trials of Vaccines	98	(2)
Additional Issues for Phase 3 Trials of Vaccines	100	(14)
Posing Research Questions for the Trial	100	(1)
Determining the Type of Vaccine Protection to Be Measured	100	(1)
Selecting an Appropriate Setting and Study Population	101	(1)
Predicting the Incidence of the Target Expected in the Comparison Group	102	(3)
Ensuring That the Source Population Is Large Enough	105	(1)
Allocating and Administering the Compared Agents	106	(2)
Detecting and Defining Outcomes for Assessing Vaccine Protection	108	(2)
Assessing Vaccine Safety	110	(1)
Determining When to Terminate Surveillance	111	(1)
Deciding on an Approach for Assessing Immune Responses to Vaccination	112	(1)
Good Clinical Practice	113	(1)
Concluding Remarks	114	(5)
References	115	(4)
4 ETHICS AND VACCINES
Ruth Macklin
Brian Greenwood
Ethical Principles	119	(1)
Vaccine Research	120	(3)
Risk--Benefit Considerations	120	(1)
Informed Consent of Research Participants	121	(1)
Justice in Research	122	(1)
Providing Access to Vaccines Proven to Be Safe and Effective	123	(2)
Public Good versus Individual Autonomy	125	(4)
References	127	(2)
5 UNDERSTANDING MICROBIAL PATHOGENESIS AS A BASIS FOR VACCINE DESIGN
Bacteria
B. Brett Finlay
Introduction	129	(2)
Toxins	131	(1)
Adhesins	132	(1)
Invasins	133	(1)
Intracellular Survival	134	(2)
Antiphagocytosis	136	(1)
Apoptosis	136	(1)
Concluding Remarks	137	(2)
References	138	(1)
Disease-Oriented Approach to the Discovery of Novel Vaccines
Jeffrey N. Weiser
Elaine I. Tuomanen
Advantages of Disease-Oriented Vaccination Strategies	139	(2)
Identification of Common Targets of Agents Causing Similar Diseases	141	(1)
Genomics Approach to Identification of Antigens Conserved among Organisms Causing Similar Diseases	141	(1)
Candidate Antigen Conserved among Bacterial Pathogens of the Respiratory Tract	142	(7)
References	146	(3)
Immunological Memory and Vaccines against Acute Cytopathic and Noncytopathic Infections
Rolf M. Zinkernagel
Introduction	149	(3)
The Roles of Early Events and Parasite Variability in Host--Parasite Relationships	152	(1)
How to Measure Immunity	153	(1)
Immunological Memory	154	(3)
Why and What Kind of Immunological Memory?	155	(1)
Immunological Memory by Neutralizing Antibodies	156	(1)
Immunity by T Cells	157	(1)
Is Protective Memory Antigen-Dependent or -Independent?	158	(2)
How Is Protective Memory Maintained by Infectious Agents or Vaccines?	160	(1)
Conclusion	160	(5)
References	161	(4)
Parasitic Diseases, with an Emphasis on Experimental Cutaneous Leishmaniasis
Pascal Launois
Heike Voigt
Alain Gumy
Abraham Aseffa
Fabienne Tacchini-Cottier
Martin Rocken
Jacques A. Louis
Introduction	165	(1)
Some Aspects of Immunity against Malaria	166	(1)
Some Aspects of Immunity to Schistosoma mansoni	167	(1)
Immunity to Leishmania	168	(5)
Murine Model of Infection with L. major	168	(1)
Mechanisms Underlying Genetically Determined Differences in Th Cell Differentiation following Infection with L. major	169	(4)
Th1 Cell Development in Resistant Mice following Infection with L. major
Th2 Cell Development in Susceptible Mice following Infection with L. major
Why Are C57BL/6 Mice Unable to Mount Early IL-4 Responses following Infection with L. major?	173	(1)
Concluding Remarks	173	(6)
References	174	(5)
6 Disease States and Vaccines: Selected Cases
Introduction
Stanley A. Plotkin
Issues in Pediatric Vaccination	179	(3)
Pertussis	179	(1)
Polio	180	(1)
Hib	180	(1)
Hepatitis B	180	(1)
Combinations	180	(1)
Pneumococcal	180	(1)
Meningococcal	181	(1)
Carrier Proteins	181	(1)
Rotavirus	181	(1)
RSV (Respiratory Syncytial Virus) and PIV (Parainfluenza Viruses)	181	(1)
MMR	181	(1)
Issues in Adult Vaccination	182	(1)
Influenza	182	(1)
Pneumococcal	182	(1)
Zoster	182	(1)
Boosters	182	(1)
Issues Concerning Newer Techniques for Vaccine Development	183	(2)
Cellular Immunity	183	(1)
Vectors	183	(1)
Nucleic Acids	183	(1)
Adjuvants	184	(1)
Genomics	184	(1)
Route of Administration	184	(1)
New Targets	184	(1)
Challenges Facing Use of Vaccines	185	(4)
Safety	185	(1)
Vaccine Cost	186	(1)
Vaccine Production	186	(1)
References	187	(2)
Polio
Ciro A. De Quadros
Introduction	189	(1)
The Disease and Its Epidemiology	190	(1)
Polio Vaccines	191	(1)
Polio and Its Global Eradication	192	(5)
History and Strategy	192	(1)
Progress to Date	193	(3)
References	196	(1)
Rubella
Jennifer M. Best
Siobhan O'shea
Description of the Disease	197	(2)
Postnatally Acquired Rubella	197	(1)
Risk of Rubella in Pregnancy	198	(1)
Congenital Rubella	198	(1)
Epidemiology	199	(1)
Prevaccine	199	(1)
Postvaccine	199	(1)
Rubella Vaccines	200	(5)
Development of Rubella Vaccines	200	(1)
Vaccine Efficacy and Immune Responses	201	(1)
Adverse Reactions	202	(1)
Contraindications	203	(1)
Vaccination in Pregnancy	203	(1)
Measles, Mumps, and Rubella (MMR) Vaccine	203	(2)
Safety of MMR Vaccine	205	(1)
Rubella Vaccination Programs and Their Impact	205	(6)
Vaccination Programs	205	(1)
Current Initiatives	206	(2)
References	208	(3)
Pertussis
Stefania Salmaso
Introduction	211	(1)
Pertussis	212	(4)
Virulence Factors	212	(2)
Adhesins
Toxins
Infection and Disease Progression	214	(1)
Frequency of Pertussis	215	(1)
Vaccination	216	(1)
Vaccines	216	(3)
Whole Cell Vaccines	216	(1)
Content
Adverse Events
Acellular Pertussis Vaccines	217	(2)
Content
Adverse Events
Efficacy	219	(1)
Open Issues	220	(5)
References	222	(3)
Rotavirus
Joseph S. Bresee
Roger I. Glass
Umesh Parashar
Jon Gentsch
Introduction	225	(1)
Rotavirus Disease and Pathophysiology	225	(1)
Epidemiology and Disease Burden	226	(1)
Virology	227	(2)
Rotavirus Strain Prevalence	229	(1)
Rationale for Immunization against Rotavirus	230	(1)
Rotavirus Vaccines	230	(7)
Nonhuman Strain Vaccines: ``Jennerian'' Approach	230	(3)
Bovine Strain RIT4237
Bovine Strain WC3
Rhesus Rotavirus Strain (RRV)
Lanzhou Lamb Rotavirus (LLR)
Human--Animal Reassortant Vaccines	233	(3)
WC3-Based Bovine--Human Reassortants
RRV-Based Rhesus--Human Reassortants and RRV-TV
UK-Based Bovine--Human Reassortant Vaccine
Human Rotavirus Strain Vaccine	236	(1)
Neonatal Human Strain Vaccines	236	(1)
M37 Strain
RV3 Strain
Indian Neonatal Strains
Other Approaches to Rotavirus Vaccines	237	(1)
Challenges to Rotavirus Vaccine Development and Introduction	237	(3)
Ensuring Vaccine Safety: Intussusception	237	(2)
Differences between Rotavirus in Developed and Developing Country Settings and Impact on Vaccine Development	239	(1)
Poor Past Performance of Rotavirus Vaccines When Tested in Developing Countries	239	(1)
Future Directions	240	(5)
References	240	(5)
AIDS Vaccines: Challenges and Prospects
Elisa I. Choi
Norman L. Letvin
Introduction	245	(1)
The Burden of HIV--AIDS	245	(1)
Biology of HIV	246	(1)
Immune Control of HIV	247	(1)
Evidence from Animal Experiments	248	(1)
HIV Vaccine Designs	248	(4)
Problems with Traditional Approaches	248	(2)
New Approaches	250	(2)
Vaccine-Elicited Clinical Protection	252	(1)
Conclusions	253	(4)
References	254	(3)
Pneumococcus, Pneumococcal Disease, and Prevention
Jill G. Hackell
Introduction	257	(1)
Organism and Nomenclature	258	(1)
Epidemiology	258	(4)
Disease	258	(3)
Nasopharyngeal Colonization	261	(1)
Pathogenesis	262	(1)
Immunology	263	(1)
Pneumococcal Conjugate Vaccine Immunology	264	(3)
Is There a Response in Children in Whom There Is No Response to Polysaccharide?	265	(1)
What Is the Isotype Profile Developed in Vaccinees?	265	(1)
Is There Evidence of Priming?	266	(1)
Is There Evidence of Affinity Maturation?	266	(1)
Is There a Functional Response?	266	(1)
Other Considerations	267	(1)
Pneumococcal Conjugate Vaccine Efficacy	267	(2)
Epidemiology of S. pneumoniae in the Conjugate Vaccine Era	269	(1)
Protection of Other Populations	270	(1)
Future Directions	270	(1)
Conclusion	271	(8)
References	272	(7)
Tuberculosis
Douglas B. Young
Introduction	279	(1)
The Old Generation of TB Vaccines	280	(2)
The New Generation of TB Vaccines	282	(3)
Immunity	282	(1)
Live Attenuated Vaccines	283	(1)
Subunit Vaccines	284	(1)
Moving New Vaccines into Humans	285	(6)
References	286	(5)
Malaria
Stephen L. Hoffman
Thomas L. Richie
Need for a Malaria Vaccine	291	(1)
Indications for a Malaria Vaccine	292	(1)
Exposure of Humans to Whole Parasites Indicates Type 1 and 2 Malaria Vaccines Are Possible	293	(1)
Why There Is Not a Malaria Vaccine	294	(4)
Targets of Protective Immune Responses	294	(2)
Immune Responses Responsible for Protection	296	(2)
Vaccine Delivery Systems	298	(1)
Current Approaches to Malaria Vaccine Development	298	(1)
Strategies for Vaccine Design	298	(1)
Current Status of Clinical Trials	299	(5)
Maximizing the Magnitude and Quality of Immune Responses to a Few Key Antigens	299	(2)
Preerythrocytic Stages
Asexual Erythrocytic Stages
Sexual Stages
Induction of Immune Responses to Multiple Antigens from Different Stages	301	(3)
Preerythrocytic Stages
Combined Preerythrocytic and Erythrocytic Stage Vaccines
Duplicate Whole-Organism-Elicited Immunity
Challenge of Designing and Executing Field Trials of Malaria Vaccines	304	(1)
Prospects for Malaria Vaccines	305	(6)
References	306	(5)
Human Papillomaviruses
Lutz Gissmann
Description of the Virus	311	(1)
Description and Epidemiology of the Diseases	312	(2)
Cutaneous Warts	312	(1)
Laryngeal Papillomas	312	(1)
Genital Warts	313	(1)
Cervical Neoplasias	313	(1)
Mechanism of Protection and Surrogate End Points	314	(6)
Immune Biology of Papillomavirus Infections	314	(1)
Animal Experiments	315	(1)
Vaccine Scenarios	316	(1)
Prophylaxis	317	(2)
Therapy	319	(1)
Current State of Play	320	(3)
References	321	(2)
Helicobacter pylori
Giuseppe Del Giudice
Rino Rappuoli
Bacterium and Infection	323	(1)
Some Antigens Important in Virulence and Pathogenesis	324	(1)
An Inefficient Natural Immune Response to H. pylori	325	(2)
Feasibility of Prophylactic and Therapeutic Vaccinations in Animal Models	327	(2)
Clinical Experience with H. pylori Vaccines: Present and Future	329	(4)
References	329	(4)
Genome-Based Approach for a Vaccine against Neisseria meningitidis
Vega Masignani
Mariagrazia Pizza
Rino Rappuoli
Neisseria meningitidis	333	(2)
Bacterium and Disease	333	(2)
Prevention	335	(1)
Reverse Vaccinology: The MenB Experience	335	(6)
Biocomputing and Whole-Genome Sequencing	335	(1)
The Reverse Vaccinology Approach	336	(1)
Genome Analysis and Antigen Selection in Neisseria meningitidis B	336	(1)
Experimental Strategy	337	(4)
Conclusions	341	(4)
References	341	(4)
7 ECONOMICS OF VACCINES: FROM VACCINE CANDIDATE TO COMMERCIALIZED PRODUCT
Amie Batson
Sarah Glass
Erica Seiguer
Introduction: Why Economics Matters	345	(1)
The Market: Vaccine Demand, Supply, and Pricing	346	(7)
Need Does Not Equal Demand	347	(1)
Who Uses and Who Buys Vaccines?	347	(1)
The Market	348	(1)
Vaccine Supply	349	(1)
Vaccine Pricing	350	(2)
Diverging Products	352	(1)
Bringing a Vaccine to Market: Costs, Risks, and Constraints	353	(5)
Baseline Costs	354	(1)
Risks	355	(2)
Research and Development
Capacity and Production
Regulatory and Licensing Issues
Production
Delivery
Sales
Each Vaccine Is Different	357	(1)
The Case of Meningococcal A Conjugate Vaccine	358	(2)
The Missed Opportunity	358	(1)
Pushing and Pulling a Meningococcal A Vaccine	359	(1)
Identifying the Hurdles	359	(1)
Push and Pull Mechanisms: Changing the Economic Equation	360	(9)
Push and Pull Mechanisms	360	(1)
Push Mechanisms	361	(2)
Direct Financing
Facilitating Research
Harmonizing Regulatory Requirements
Tax Credits for Vaccine Research
Pull Mechanisms	363	(3)
Accelerating the Uptake of Existing Vaccines
Prizes and Tournaments
Extending and Transferring Patents
Copayments
Differential (Tiered) Pricing
Market Assurances
Intellectual Property Right (IPR) Enforcement--Protection
Tax Credits for Vaccine Sales
Implementing Push--Pull Mechanisms: Public--Private Partnerships	366	(3)
Next Steps and New Approaches	369	(2)
References	369	(2)
8 VACCINE SAFETY: REAL AND PERCEIVED ISSUES
Neal A. Halsey
Introduction	371	(1)
How Vaccines Are Evaluated for Causal Associations with Adverse Events	372	(3)
Identification of Vaccine Agents in Affected Tissues	372	(1)
Epidemiologic Studies	373	(1)
Misunderstanding Causality Assessment	374	(1)
Types of Adverse Events Caused by Vaccines	375	(5)
Injection Process	375	(2)
Pain
Fainting
Tissue Injury
Provocation Polio
Errors in Reconstitution
Contamination of Multidose Vials
Incomplete Inactivation of Vaccine Agent	377	(1)
Replication of Live Vaccine Agent	377	(1)
Inadvertent Contamination of Vaccines with Other Live Agents	378	(1)
Direct Effect of Vaccine Component	379	(1)
Host Immune Response to Vaccine Component	379	(1)
Immune Deficiency Disorders	380	(2)
HIV Infection	381	(1)
Misunderstandings and False Accusations Regarding the Safety of Commonly Used Vaccines	382	(2)
Hepatitis B, Multiple Sclerosis, and Other Demyelinating Diseases	382	(1)
Type 1 Diabetes Mellitus and Vaccines	383	(1)
MMR and Autism	383	(1)
Conclusion	384	(8)
References	385	(7)
9 INTRODUCTION OF NEW VACCINES IN THE HEALTHCARE SYSTEM
Edward Kim Mulholland
Bjarne Bjorvatn
The Decision Process	392	(14)
Organizational Features	392	(1)
Scientific Decision-Making Process: Assessment of Disease Burden and Cost Effectiveness	392	(4)
Assessment of Individual Vaccines: Efficacy and Effectiveness	396	(2)
Antimicrobial Resistance	398	(1)
Vaccine Safety	399	(3)
Adaptability to National Immunization Schedules	402	(2)
Vaccine Price	404	(1)
The Role of the Private and Nongovernment Sectors	405	(1)
Case Studies	406	(2)
Case Study 1: Introduction of Hib Vaccine into Australia	406	(1)
Case Study 2: Introduction of Hepatitis B Vaccine into Vietnam	407	(1)
Concluding Remarks	408	(4)
References	409	(3)
10 FUTURE CHALLENGES FOR VACCINES AND IMMUNIZATION
Paul-Henri Lambert
Barry R. Bloom
Cross-Cutting Issues in Vaccines against Infectious Diseases	412	(2)
Vaccines for Noninfectious Diseases: A New Frontier for Vaccine Research	414	(6)
Requirements Related to New Vaccination Strategies	420	(3)
Public Acceptance of Vaccination	423
References	424