Vaccines. From Concept To Clinic

Vaccines: From Concept to Clinic: A Guide to the Development and Clinical Testing of Vaccines for Human Use......Page 1
About the Editors......Page 4
Foreword......Page 5
Preface......Page 8
Contributors......Page 10
Table of Contents......Page 12
IDENTIFICATION OF THE DISEASES FOR WHICH VACCINES ARE NEEDED......Page 13
Live Attenuated Vaccines......Page 14
Subunit Vaccines......Page 16
IDENTIFICATION AND SELECTION OF PROTECTIVE ANTIGENS......Page 18
ANIMAL MODELS AND VACCINE DELIVERY......Page 20
WHAT TYPES OF IMMUNE RESPONSES?......Page 21
REFERENCES......Page 24
Animal Models and Animal Test Systems......Page 30
Selecting an Animal Species for Use......Page 32
Nonhuman Primates in Vaccine Development......Page 33
ANIMAL CARE CONSIDERATIONS......Page 34
USE OF RODENTS AS ANIMAL MODELS......Page 35
Infectious Challenge......Page 36
Immunologic Considerations......Page 37
NONHUMAN PRIMATE MODELS TO EVALUATE VACCINE IMMUNOGENICITY......Page 39
Considerations for Employing Primate Species......Page 40
Nonhuman Primates as Models for Infectious Diseases......Page 41
Comparative Immunology and Reproductive Physiology......Page 42
ENDOGENOUS AGENTS AS RISK FACTORS FOR ANIMAL MODELS......Page 44
OPTIMIZATION AND ALTERNATIVES TO THE USE OF ANIMALS......Page 45
REFERENCES......Page 47
PURPOSE OF ASSAY STANDARDIZATION AND VALIDATION......Page 54
SELECTION OF SEROLOGIC METHODS......Page 56
ASSAY DESIGN CONSIDERATIONS......Page 58
Antigens......Page 59
SERA......Page 62
Reference Standard Serum......Page 65
Quality Control Sera......Page 67
Subject Sera......Page 68
ASSAY CONDITIONS......Page 70
CORRELATIONS OF IMMUNOASSAYS TO FUNCTIONAL ASSAYS......Page 72
CONCLUSIONS......Page 74
REFERENCES......Page 75
INTRODUCTION......Page 87
GENERATING A LOT OF VACCINE FOR A PHASE 1 CLINICAL TRIAL......Page 88
Quantity......Page 90
Formulation......Page 91
Container Size/Doses......Page 92
Stability......Page 93
Vaccine Preparation......Page 94
SUMMARY AND SUBMISSION OF IND APPLICATION......Page 95
ACKNOWLEDGMENTS......Page 96
REFERENCES......Page 97
CLINICAL TRIAL DEFINITIONS......Page 98
PROCEDURES AND REQUIREMENTS FOR FILING AN IND APPLICATION......Page 99
SOURCES OF INFORMATION......Page 100
PREPARING THE IND APPLICATION......Page 101
INVESTIGATOR’S BROCHURE......Page 104
a Study Protocol......Page 105
b Investigator Data, c Facilities Data, and d Institutional Review Board Data......Page 108
CHEMISTRY, MANUFACTURING, AND CONTROL DATA......Page 112
PREVIOUS HUMAN EXPERIENCE AND ADDITIONAL INFORMATION......Page 114
COMPLETING THE IND FORM......Page 115
INTRODUCTION......Page 116
IND CONTENT AND FORMAT: ORIGINAL SUBMISSION......Page 117
Manufacturing Information......Page 120
2. General Safety......Page 121
Product Characterization......Page 122
Lot Release......Page 123
Safety and Toxicity Studies......Page 124
CLINICAL TRIALS......Page 125
Overview of the IND Process......Page 126
Clinical Hold......Page 127
Safety Reports......Page 128
Manufacturing......Page 129
Protocols......Page 130
Guidance Documents......Page 131
1. Pre-IND Meetings......Page 132
2. Other Meetings......Page 133
REFERENCES......Page 134
INTRODUCTION......Page 136
POLICIES AND LAWS AFFECTING TECHNOLOGY TRANSFER......Page 137
THE MECHANISMS OF TECHNOLOGY TRANSFER......Page 139
MATERIAL TRANSFER AGREEMENTS MTAs......Page 141
SPONSORED-RESEARCH AGREEMENT......Page 142
COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT CRADA......Page 144
INVENTIONS......Page 147
INVENTORSHIP......Page 148
PATENTS......Page 149
Enabling:......Page 151
THE PATENT PROCESS......Page 153
PROVISIONAL APPLICATION......Page 155
EFFECTS OF PUBLIC DISCLOSURES ON PATENTS......Page 156
RECORD KEEPING......Page 157
INVENTION RIGHTS......Page 158
LICENSING......Page 159
ROYALTY AND EQUITY......Page 162
FEDERAL TECHNOLOGY PROGRAMS......Page 163
TECHNOLOGY TRANSFER OFFICES......Page 164
CONCLUSION......Page 166
Appendix A: Technology Transfer Terminology......Page 167
Appendix B: Material Transfer Agreement Provider......Page 171
Materials Receipt Agreement......Page 174
Appendix C......Page 176
Appendix D: Small-Business Innovation Research SBIR Program......Page 178
Appendix E: Small Business Technology Transfer Research STTR Program......Page 180
REFERENCES......Page 181
IDENTIFICATION OF TRANSMISSION-BLOCKING TARGET ANTIGENS......Page 184
ISOLATION OF THE GENE ENCODING Pfs25......Page 185
INDUSTRIAL COLLABORATION......Page 186
Subunit Approaches......Page 187
Good Manufacturing Practices......Page 188
THE FUTURE: PRIME-BOOST AND FUSION PROTEINS......Page 189
REFERENCES......Page 190
Malignant Transformation of Cultured Cells with Human Adenovirus and Herpes Simplex Virus......Page 192
MOTIVATIONS FOR AND PROBLEMS IN THE DEVELOPMENT OF A LIVE VARICELLA VACCINE......Page 193
PRIMARY ISOLATION OF VACCINE VIRUS......Page 194
RATIONALE FOR AND DESIGN OF A LIVE VARICELLA VACCINE......Page 195
CLINICAL TRIALS WITH VACCINES PREPARED IN HUMAN DIPLOID CELLS......Page 196
VACCINATION OF CHILDREN WITH MALIGNANT DISEASES......Page 197
VIEWPOINTS REGARDING LIVE VARICELLA VACCINE AFTER INITIAL CLINICAL TRIALS......Page 198
CLINICAL VACCINE TRIALS IN THE UNITED STATES AND EUROPE......Page 199
DETECTION OF VIREMIA BEFORE AND AT THE ONSET OF CHICKENPOX: HERPES ZOSTER AND VARICELLA VACCINE......Page 200
FURTHER CLINICAL STUDIES IN THE UNITED STATES PARTICULARLY ON THE INCIDENCE OF ZOSTER AFTER VACCINATION......Page 202
REFERENCES......Page 203
Acronyms and Abbreviations......Page 208