Manmohan Singh & Indresh K. Srivastava 
Development of Vaccines 
From Discovery to Clinical Testing

Development of Vaccines: From Discovery to Clinical Testing outlines the critical steps, and analytical tools and techniques, needed to take a vaccine from discovery through a successful clinical trial. Contributions from leading experts in the critical areas of vaccine expression, purification, formulation, pre-clinical testing and regulatory submissions make this book an authoritative collection of issues, challenges and solutions for progressing a biologic drug formulation from its early stage of discovery into its final clinical testing. A section with details and real-life experiences of toxicology testing and regulatory filing for vaccines is also included.

Table of Content

PREFACE ix

CONTRIBUTORS xi

PART 1 IMMUNOGEN DESIGN 1

1 MICROBIAL VACCINE DESIGN: THE REVERSE VACCINOLOGY APPROACH
3

Roberto Rosini, Michele A. Barocchi, and Rino Rappuoli

2 DESIGN AND DEVELOPMENT OF RECOMBINANT VACCINES WITH VIRAL
PROPERTIES 19

Gerd Lipowsky and Martin F. Bachmann

3 TOOLS FOR VACCINE DESIGN: PREDICTION AND VALIDATION OF HIGHLY
IMMUNOGENIC AND CONSERVED CLASS II EPITOPES AND DEVELOPMENT OF
EPITOPE-DRIVEN VACCINES 65

Anne S. De Groot, Matthew Ardito, Ryan Tassone, Paul Knopf,
Leonard Moise, and William Martin

PART 2 VACCINE PLATFORMS 95

4 VIRUS-LIKE PARTICLE VACCINES: ADVANTAGES AND CHALLENGES
97

Ted M. Ross, Nitin Bhardwaj, Hermancia S. Eugene, Brendan M.
Giles, Sean P. Mc Burney, Shannan L. Rossi, Kirsten Schneider-Ohrum,
and Xian-chun Tang

5 DESIGN PLATFORMS OF NANOCAPSULES FOR HUMAN THERAPEUTICS OR
VACCINES 125

Masaaki Kawano, Li Xing, Kit S. Lam, Hiroshi Handa, Tatsuo
Miyamura, Susan Barnett, Indresh K. Srivastava, and R. Holland
Cheng

6 DESIGNING IMMUNOGENS FOR VACCINE DEVELOPMENT IN REFERENCE TO
HIV 141

Aemro Kassa, Zohar Biron-Sorek, Pampi Sarkar, and Indresh K.
Srivastava

7 EXPRESSION AND PURIFICATION OF RECOMBINANT PROTEINS FOR
VACCINE APPLICATIONS 185

Carlo Zambonelli, Deeann Martinez-Guzmann, and Indresh K.
Srivastava

8 DNA VACCINES FOR INFECTIOUS DIESASE 215

Samuel Stepenson, Manmohan Singh, and Indresh K.
Srivastava

9 DEVELOPING STABLE CELL LINES FOR THE PRODUCTION OF VACCINE
ANTIGENS 243

Xiaotian Zhong, Zhijian Lu, Richard Zollner, Jimin Zhang, Emily
Braunstein, Narender Kalyan, and Maninder Sidhu

PART 3 CHARACTERIZATION OF IMMUNOGENS 261

10 SPECTROSCOPY OF VACCINES 263

C. Russell Middaugh and Sangeeta B. Joshi

11 BIOPHYSICAL CHARACTERIZATION OF PROTEIN ANTIGENS WITHIN
VACCINE FORMULATIONS 293

Padma Malyala, Derek O’Hagan, and Manmohan Singh

PART 4 FORMULATION OPTIMIZATION AND STABILITY
EVALUATION 305

12 STRUCTURAL CHARACTERISTICS PREDICT THE STABILITY OF HIV
307

Zohar Biron-Sorek, Yide Sun, Elaine Kan, Jeanne Flandez, Michael
Franti, Jeffrey Ulmer, Susan Barnett, and Indresh K.
Srivastava

13 SELECTION OF OPTIMAL ADJUVANTS AND PRODUCT FACTORS THAT
AFFECT VACCINE IMMUNOGENICITY 327

Wei Wang and Manmohan Singh

14 LYOPHILIZATION AND STABILIZATION OF VACCINES 385

James Chesko, Chris Fox, Tim Dutill, Thomas Vedvick, and Steve
Reed

15 EFFECT OF BUFFERS AND STABILIZERS ON VACCINE STABILITY AND
EFFICACY 399

Shireesh P. Apte and Sydney O. Ugwu

PART 5 CLINICAL AND MANUFACTURING ISSUES 415

16 SELECTION OF FINAL PRODUCT CONTAINERS 417

Luis Baez and Adrian Distler

17 FROM THE LAB TO THE CLINIC: FILING A PHASE I IND FOR AN
INVESTIGATIONAL VACCINE 437

Kenneth G. Surowitz

INDEX 451

About the author

Manmohan Singh, Ph D, is currently working as the Global Head
of Vaccine Formulation Science at Novartis Vaccines and Diagnostics
in Cambridge, Massachusetts. Dr. Singh is a well-known expert in
the areas of vaccine formulations and adjuvant research and has
been working in vaccine R&D for the last twenty years. He has
authored over 100 peer-reviewed manuscripts, review articles, and
book chapters in this area. Dr. Singh is on the editorial board of
seven international journals and has contributed to organizing
several international vaccine conferences. He is also the editor of
Vaccine Adjuvants and Delivery Systems (also published by Wiley).

Indresh K. Srivastava, Ph D, is recognized as an expert in
the field of vaccine research, particularly immunogen design,
purification, and characterization of vaccines. He has been working
in the field for more than twenty-five years; has published more
than seventy-five scientific papers in peer-reviewed journals; and
authored several reviews and book chapters. In addition, he has
served on NIH special emphasis study sections focused on HIV
Vaccines. He is on the editorial board of Current HIV Research, and
is reviewer for ten international journals. After spending more
than twelve years at Chiron/Novartis, Dr. Srivastava has joined the
Vaccine Research Institute, NIAID/NIH, to lead the purification and
analytical development of vaccine candidates. Prior to joining
Chiron, he was an assistant professor (research) in microbiology
and immunology, Medical College of Pennsylvania, Philadelphia.