Immunopotentiators in Modern Vaccines

1st Edition - December 13, 2005
Editors: Virgil Schijns, Derek O'Hagan
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 0 8 8 4 0 3 - 2
eBook ISBN:
9 7 8 - 0 - 0 8 - 0 4 5 7 2 1 - 5

Immunopotentiators in Modern Vaccines provides an in-depth insight and overview of a number of most promising immunopotentiators in modern vaccines. In contrast to existing books… Read more

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Immunopotentiators in Modern Vaccines provides an in-depth insight and overview of a number of most promising immunopotentiators in modern vaccines. In contrast to existing books on the subject it provides recent data on the critical mechanisms governing the activity of vaccine adjuvants and delivery systems. Knowledge of immunological pathways and scenarios of the cells and molecules involved is described and depicted in comprehensive illustrations.

Preface
List of contributors
Part I: Perspective on immunological mechanisms underlying adjuvant activity
- Chapter 1: Unraveling “the immunologist’s dirty little secret”
  - Publisher Summary
  - Introduction
  - Adjuvants provide start signals for immune reactivity and guide the response to an acceptable magnitude
  - Regulation of immune responses by antigen deliverance (signal I)
  - Facilitation of signal 1
  - Regulation of signal 2
  - Facilitation of signal 2
  - Adjuvants provide signal 3, regulating the quality of immunity
  - Outlook
  - Acknowledgments
Part II: Host-derived immunopotentiators
- Chapter 2: Dendritic cells as targets and tools in vaccines
  - Publisher Summary
  - Introduction
  - DCs as targets for modern vaccines
  - New adjuvants and DCs
  - DCs as tools for the development of therapeutic vaccines
  - Final remarks
  - Acknowledgments
- Chapter 3: Host-derived molecules as adjuvants
  - Publisher Summary
  - Introduction
  - Cytokines as immunological adjuvants
  - C3d-based adjuvants
  - Heat shock proteins
  - Host cell surface proteins
  - Special applications of host-derived adjuvants
  - Concluding remarks
  - Acknowledgments
Part III: Natural and synthetic immunopotentiators
- Chapter 4: Innate immune mechanisms and the identification of immune potentiators as vaccine adjuvants
  - Publisher Summary
  - Introduction
  - Innate immunity: a trigger point for the immune system
  - Pathogen-associated molecular patterns and pattern recognition receptors
  - Innate immunity conditions the host for subsequent adaptive immunity
  - Adjuvants in vaccine research
  - Structure and function of TLRs and Nods
  - Ligands of TLRs and Nods
  - Signaling through PRRs
  - Small-molecule immune potentiators: the future of adjuvants?
  - Drug discovery strategies for immune potentiators
  - Random screening based on functional outcome
  - Targeted screening
  - Future directions
  - Acknowledgment
- Chapter 5: CpG oligodeoxynucleotides as vaccine adjuvants
  - Publisher Summary
  - Introduction
  - CpG oligodeoxynucleotides
  - CpG as a vaccine adjuvant
  - Safety of CpG ODN as a vaccine adjuvant
  - Conclusions
- Chapter 6: Toll-like receptor 4 agonists as vaccine adjuvants
  - Publisher Summary
  - Introduction
  - Toll-like receptors: the missing link between innate and adaptive immunity
  - MPL and AGPs:TLR4 agonists as vaccine adjuvants
  - Clinical experience with TLR4 agonists as adjuvants
  - Safety of TLR agonists as vaccine adjuvants
  - Regulatory approval of the first TLR agonist as a vaccine adjuvant
  - Mechanism (s) of action of TLR4 agonists
  - TLR4 agonists as nonspecific immunomodulators
  - Rapid-acting vaccines
  - Concluding remarks
- Chapter 7: Immunomodulatory adjuvants from Quillaja saponaria
  - Publisher Summary
  - Introduction
  - Structure of Quillaja saponaria saponins
  - Saponin purification and development
  - Adjuvant activity of saponins
  - Structure/function studies
  - Saponin adjuvants in clinical trials
  - Conclusions
  - Acknowledgments
Part IV: Particulate immunopotentiators and delivery systems
- Chapter 8: Microparticles as vaccine delivery systems
  - Publisher Summary
  - Introduction
  - Role of adjuvants in vaccine development
  - Immunopotentiator adjuvants
  - Particulate vaccine delivery systems
  - Alternative routes of immunization
  - Adjuvants for therapeutic vaccines
  - Future of microparticles for vaccine delivery
  - Acknowledgments
- Chapter 9: MF59: a safe and potent adjuvant for human use
  - Publisher Summary
  - Introduction
  - Initial development of MF59 adjuvant
  - Mechanism of action of MF59
  - Composition of MF59
  - Manufacturing of MF59
  - Preclinical experience with MF59
  - Clinical experience with MF59 adjuvant
  - Combination of MF59 with immunopotentiators
  - Use of MF59 in prime/boost settings
  - Future perspectives on the use of MF59
- Chapter 10: Development and evaluation of AS04, a novel and improved adjuvant system containing MPL and aluminum salt
  - Publisher Summary
  - Introduction
  - AS04 adjuvant system
  - AS04 formulation process
  - MPL dose selection
  - Safety aspects of adjuvants for use in vaccines
  - Examples of AS04-based vaccines
  - Summary
  - Abbreviations
  - Acknowledgments
- Chapter 11: Virosomes for vaccine delivery
  - Publisher Summary
  - Introduction
  - Development of the IRIV concept
  - Incorporation of antigens into IRIVs
  - IRIVs and registered vaccines
  - IRIVs and malaria prophylaxis
  - IRIVs and cancer therapy
- Chapter 12: The ISCOMATRIX™ adjuvant
  - Publisher Summary
  - Introduction
  - Preparation and properties of ISCOMATRIX™ adjuvant
  - Nonclinical studies
  - Clinical experience
  - Mechanism of Action
  - Summary
  - Acknowledgments
- Chapter 13: Mineral adjuvants
  - Publisher Summary
  - Introduction
  - Preparation and crystalline structure of mineral adjuvants
  - Application of mineral adjuvants
  - Dosing mineral adjuvants
  - Mechanisms of adjuvant activity
  - Mineral adjuvants and stimulation of IgE
  - Limitations to the applicability of mineral adjuvants
  - In vivo clearing of aluminum and calcium adjuvants
  - Side effect profile of mineral adjuvants
  - Conclusion
Part V: Mucosal/nonparenteral adjuvants
- Chapter 14: Mucosal adjuvants based on cholera toxin and E. coli heat-labile enterotoxin
  - Publisher Summary
  - Introduction
  - The need for mucosal vaccines and adjuvants
  - Cholera toxin and E. coli heat-labile enterotoxin as mucosal immunogens and adjuvants
  - Development of nontoxic derivatives as mucosal adjuvants
  - CTand CTB as adjuvants for dendritic cell vaccination
  - Mucosal immunotherapy based on cholera toxin B subunit
  - Conclusions
- Chapter 15: Transcutaneous immunization using the heat-labile enterotoxin of E. coli as an adjuvant
  - Publisher Summary
  - Introduction
  - Background
  - Molecular structure
  - Trafficking within the cell
  - Cell biology
  - Safety and efficacy of bAREs
  - Systemic and mucosal responses
  - Delivery optimization
  - Regulatory considerations
  - Comparison with other skin delivery technologies
  - Summary
  - Acknowledgments
Part VI: Th-1/CTL adjuvants
- Chapter 16: T cell adjuvants and novel strategies for their identification
  - Status of T cell adjuvant testing in humans
  - T lymphocyte polarization
  - Implications for vaccine design
  - New strategies to screen synthetic T cell adjuvants
  - Conclusions
Part VII: Adjuvants in noninfectious disease vaccines
- Chapter 17: Vaccination to treat noninfectious diseases: surveying the opportunities
  - Publisher Summary
  - Introduction
  - Adjuvants in antibody-based immunotherapy
  - Adjuvants to stimulateT cell immunity
  - Adjuvants inducing immune deviation or immunosuppression
  - Summary and conclusions
Part VIII: Clinical practice
- Chapter 18: Clinical evaluation of adjuvants
  - Publisher Summary
  - Introduction
  - Definitions
  - Characteristics of an ideal adjuvant
  - Components of rational adjuvant development
  - Regulatory issues
  - Adjuvants used in licensed vaccines for humans
  - Experimental adjuvants in humans
  - Summary and conclusion
- Chapter 19: Regulatory considerations in the nonclinical safety assessment of adjuvanted preventive vaccines
  - Publisher Summary
  - Introduction
  - Definitions
  - Current status of relevant, global regulatory guidance and initiatives
  - Relevant US (FDA) regulatory requirements and considerations
  - Toxicity studies for preventive vaccines
  - Special considerations for adjuvanted vaccines
  - Conclusions
  - Additional information
  - Acknowledgments
Index

Virgil Schijns

Dr. Virgil E.J.C. Schijns is special guest Professor in Cell Biology & Immunology group, Wageningen University, 6708 WD Wageningen, The Netherlands. Dr. Schijns received his Ph.D. degree at Utrecht University in 1990. Recent professional appointments are Chief Scientific Officer at ERC in Belgium and The Netherlands, (2011 to present); Chief Technology Officer, Vice-president at a small biotech spin-off from Utrecht University (2008 to 2011); Special professor immune Intervention, Wageningen University and Research center (2008 to present); Special Professor in Immunology and Virology at North Carolina State University (NCSU), Raleigh. Department of Population Health and Pathobiology (2002 to present) and Head of Department for Vaccine Technology and Immunology (VTI), AKZO NOBEL (1999 to 2008).

Affiliations and expertise

Visiting professor, Strathclyde University, Glasgow, UK and Professor, Cell Biology and Immunology Group; Special Professor in Immunology and Virology at North Carolina State University, USA

Derek O'Hagan

Dr. Derek O’Hagan was the Global Head of Vaccine Chemistry and Formulation Research for Novartis Vaccines, based in Cambridge, MA until acquisition by GSK in March, 2015. He managed research teams (~50 total staff) in Cambridge and Siena, Italy. He originally qualified as a pharmacist in the UK, and is a former academic researcher who has worked on vaccine delivery in the industry since 1993. He was formerly a Lecturer in Drug Delivery at the Department of Pharmaceutical Sciences, University of Nottingham, UK, and received research funding from the World Health Organization, The Wellcome Trust and the Medical Research Council. He was recruited into the US in 1993, and moved to progress basic research into clinical evaluation, then subsequently worked on several vaccine delivery systems that were evaluated in the clinic, including novel adjuvants, nucleic acid vaccines and needle free vaccines. In the mid 1990’s, Dr. O’Hagan worked on the emulsion adjuvant MF59, which is now included in a licensed flu vaccine in more than 40 countries and is progressing towards licensure in the US. He has co-authored >140 original research publications, >60 book chapters and reviews and I am a named inventor on >60 filed patents. He was awarded the Conference Science medal of the Royal Pharmaceutical Society of Great Britain in 1997, and the Young Investigator Research Achievement Award of the Controlled Release Society in 1999. He was also named as the ‘most inventive scientist’ in Chiron in 2004 and was the lead author on the most cited paper in ‘Vaccine’ 2008-10. Dr. O’Hagan served on the Board of Scientific Advisors for the Controlled Release Society and is a Fellow of the American Association of Pharmaceutical Scientists.

Affiliations and expertise

Vaccine Adjuvants and Delivery Chiron Corporation, CA, USA

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

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Immunopotentiators in Modern Vaccines

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Virgil Schijns

Derek O'Hagan