Development of Vaccines: From Discovery to Clinical Testing

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 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. 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 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