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.

Manmohan Singh, PhD, 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, PhD, 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.

PREFACE ix

CONTRIBUTORS xi

PART 1IMMUNOGEN 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 2VACCINE PLATFORMS 95

4 VIRUS-LIKE PARTICLE VACCINES: ADVANTAGES AND CHALLENGES 97
Ted M. Ross, Nitin Bhardwaj, Hermancia S. Eugene, Brendan M. Giles, Sean P. McBurney, 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 3CHARACTERIZATION 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 OHagan, and Manmohan Singh

PART 4FORMULATION 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 5CLINICAL 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