Table Of ContentAdvances in Delivery Science and Technology
Camilla Foged
Thomas Rades
Yvonne Perrie
Sarah Hook Editors
Subunit
Vaccine
Delivery
Advances in Delivery Science and Technology
Series Editor
Michael J. Rathbone
More information about this series at h ttp://www.springer.com/series/8875
Camilla Foged (cid:129) Thomas Rades
Yvonne Perrie (cid:129) Sarah Hook
Editors
Subunit Vaccine Delivery
Editors
Camilla Foged Thomas Rades
Department of Pharmacy Department of Pharmacy
Faculty of Health and Medical Sciences Faculty of Health and Medical Sciences
University of Copenhagen University of Copenhagen
Copenhagen , Denmark Copenhagen , Denmark
Yvonne Perrie Sarah Hook
Pharmacy School Division of Health Sciences
School of Life and Health Sciences School of Pharmacy
Aston University University of Otago
Birmingham , UK Dunedin , New Zealand
ISSN 2192-6204 ISSN 2192-6212 (electronic)
ISBN 978-1-4939-1416-6 ISBN 978-1-4939-1417-3 (eBook)
DOI 10.1007/978-1-4939-1417-3
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2014954730
© Springer Science+Business Media New York 2015
T his work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection
with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and
executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this
publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s
location, in its current version, and permission for use must always be obtained from Springer.
Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations
are liable to prosecution under the respective Copyright Law.
T he use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for
any errors or omissions that may be made. The publisher makes no warranty, express or implied, with
respect to the material contained herein.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
Pref ace
The objective of this book is to compile the concepts essential for the understanding
of the pharmaceutical science and technology associated with the delivery of subunit
vaccines. The book’s goal is to provide a comprehensive overview of the scientifi c
and regulatory challenges facing scientists who research and develop subunit vac-
cines. The scope of the book is wide. It is written in a manner that will enlighten
newcomers to the fi eld (e.g., Ph.D. students or experienced scientist switching fi elds)
yet provides an in-depth knowledge that would benefi t a skilled worker in the fi eld.
A signifi cant improvement in the safety of modern vaccines has been the develop-
ment of subunit vaccines, as these are composed of very well-defi ned and highly
pure components, often recombinant proteins. However, since protein-based anti-
gens in general are weakly immunogenic by themselves, co-administration of adju-
vants is required to induce potent and persistent specifi c immune responses. In recent
years, there has been substantial progress in the discovery of new effi cient adjuvants
for subunit vaccines that are often classifi ed into delivery systems (e.g., liposomes,
emulsions, and polymeric nanoparticles) and immunopotentiating compounds that
constitute pathogen-associated molecular patterns, such as the toll-like receptor
ligands. The combination of delivery systems and immunopotentiators has created
highly effi cacious adjuvants due to concomitant enhanced antigen delivery and
potent stimulation of immunity. Many of these adjuvants are of a particulate nature
and mimic the structure and/or composition of microbes in a reductionist fashion.
Examples are liposomes, polymeric nanoparticles, emulsions, and virus- like parti-
cles. However, there are a substantial number of pharmaceutical challenges associ-
ated with the subunit vaccine development process due to the complex nature of the
antigen–adjuvant combinations. These challenges will be presented and discussed in
this book.
Copenhagen, Denmark Camilla Foged
Copenhagen, Denmark Thomas Rades
Birmingham, UK Yvonne Perrie
Dunedin, New Zealand Sarah Hook
v
Contents
Part I Background
1 Immunological Background ................................................................... 3
Andrew J. Highton and Roslyn A. Kemp
2 Classification of Vaccines ....................................................................... 15
Rie S. Kallerup and Camilla Foged
Part II Delivery Systems for Subunit Vaccines
3 Aluminum Adjuvants: Basic Concepts and Progress
in Understanding ..................................................................................... 33
Erik B. Lindblad
4 Emulsions as Vaccine Adjuvants ........................................................... 59
Ruchi R. Shah , Luis A. Brito , Derek T. O’Hagan ,
and Mansoor M. Amiji
5 The Application of Liposomes as Vaccine Adjuvants .......................... 77
Elisabeth Kastner , Signe T. Schmidt , Alexander Wilkinson ,
Dennis Christensen , and Yvonne Perrie
6 Developing Bilayer-Based Delivery Systems for Oral Delivery
of Subunit Vaccines ................................................................................. 95
Jitinder S. Wilkhu and Yvonne Perrie
7 Cubosomes: Structure, Preparation and Use as an Antigen
Delivery System ....................................................................................... 125
Shakila B. Rizwan and Ben J. Boyd
8 ISCOMs as a Vaccine Delivery System ................................................. 141
Hanne M. Nielsen , Henriette B. Hübschmann ,
and Thomas Rades
vii
viii Contents
9 Virus-Like Particles, a Versatile Subunit Vaccine Platform ............... 159
Braeden Donaldson , Farah Al-Barwani , Vivienne Young ,
Sarah Scullion , Vernon Ward , and Sarah Young
10 Polymeric Particulates for Subunit Vaccine Delivery .......................... 181
Thomas Schuster , Martin Nussbaumer , P atric Baumann ,
Nico Bruns , Wolfgang Meier , and Anja Car
11 Gels as Vaccine Delivery Systems .......................................................... 203
Sarah Gordon
12 Implants as Sustained Release Delivery Devices
for Vaccine Antigens ............................................................................... 221
Julia Engert
13 Dendritic Cell-Based Vaccines ............................................................... 243
Olivier Gasser and Ian F. Hermans
Part III Delivery Routes, Devices and Dosage Forms
14 Parenteral Vaccine Administration: Tried and True ........................... 261
Pål Johansen and Thomas M. Kündig
15 Nasal Administration of Vaccines .......................................................... 287
Regina Scherließ
16 Pulmonary Administration of Subunit Vaccines .................................. 307
Wouter F. Tonnis , Anke L. W. Huckriede , Wouter L.J. Hinrichs ,
and Henderik W. Frijlink
17 Vaginal Delivery of Subunit Vaccines .................................................... 331
Deborah Lowry
18 Transcutaneous Immunization .............................................................. 347
Teerawan Rattanapak , Camilla Foged , and Sarah Hook
Part IV Pharmaceutical Analysis and Quality Control of Vaccines
19 Pharmaceutical Analysis and Quality Control of Vaccines................. 373
Michele Pallaoro
20 The Physical Analysis of Vaccines ......................................................... 385
Yuan Cheng , Justin C. Thomas , Sangeeta B. Joshi , David B. Volkin ,
and C. Russell Middaugh
21 Characterizing the Association Between Antigens
and Adjuvants ......................................................................................... 413
Mette Hamborg and Camilla Foged
Index ................................................................................................................. 427
Contributors
Farah Al-Barwani D epartment of Microbiology and Immunology, S chool of
Medical Sciences, University of Otago , D unedin , New Zealand
D epartment of Pathology, S chool of Medicine, University of Otago, D unedin,
New Zealand
Mansoor M. Amiji Department of Pharmaceutical Sciences, School of Pharmacy,
Northeastern University , Boston , MA , USA
Patric Baumann Department of Chemistry , University of Basel , Basel , Switzerland
Ben J. Boyd Faculty of Pharmacy and Pharmaceutical Sciences , Monash
University , Melbourne , VIC , Australia
Luis A. Brito Novartis Vaccines & Diagnostics , Cambridge , MA , USA
Nico Bruns Department of Chemistry , University of Basel , Basel , Switzerland
Adolphe Merkle Institute, University of Fribourg , Marly , Switzerland
Anja Car Department of Chemistry , University of Basel , Basel , Switzerland
Yuan Cheng Department of Discovery Pharmaceutics, Pharmaceutical Candidate
Optimization, Bristol-Myers Squibb, Princeton, NJ, USA
Dennis Christensen D epartment of Infectious Disease Immunology, V accine
Adjuvant Research, Statens Serum Institut , Copenhagen , Denmark
Braeden Donaldson Department of Microbiology and Immunology , School of
Medical Sciences, University of Otago , D unedin , New Zealand
D epartment of Pathology, S chool of Medicine, University of Otago, D unedin,
New Zealand
Julia Engert D epartment of Pharmacy, Pharmaceutical Technology and
Biopharmaceutics , Ludwig-Maximilians-University Munich , Munich , Germany
ix
