ABSTRACT
Abstract .................................................................................................................. 186 7.1 Introduction: Background and Driving Forces ............................................. 186
7.1.1 Inactivated/Attenuated Pathogen Vaccines ....................................... 186 7.1.2 Protein Vaccines ............................................................................... 187 7.1.3 Genetic or DNA Vaccines or Gene-Based Vaccines ........................ 187 7.1.4 Prime-Boost Combinations of Gene-Based and Protein-Based
Vaccines ............................................................................................ 187 7.1.5 Viral Vectors as Gene-Based Vaccines ............................................ 188 7.1.6 Adenoviruses as Vaccines ................................................................ 188 7.1.7 Accidental Proof of Principle for the Use of Ads as Gene-Based
Vaccines ............................................................................................ 188 7.1.8 Ads as Gene-Based Vaccines ........................................................... 189
7.2 Adpples and Oranges .................................................................................... 189 7.3 Ad Vectors with Different DNA and Virus Replication Capacities ............. 190
7.3.1 RC-Ad Vaccines Amplify Antigen Transgenes ................................ 190 7.3.2 RC-Ad Vaccines Amplify Infectious Progeny Viruses and
Can Risk Adenovirus Infections ....................................................... 191 7.3.3 RD-Ads: First Generation ΔE1, ΔE3 Vectors ................................... 191 7.3.4 RD Helper-Dependent Ad Vectors to Evade Vector-Specific
T-Cell Responses .............................................................................. 191 7.3.5 Head to Head Comparisons of RC and RD-Ad Vaccines ................ 192 7.3.6 Head to Head Comparisons of RC, RD, and HD-Ad Vaccines ........ 192 7.3.7 Single-Cycle Ad Vaccines: Transgene Replication without
Virus Production ............................................................................... 193 7.3.8 Amplified Production of Functional Influenza Antibodies
by SC-Ad........................................................................................... 193 7.4 Pre-existing and Vector-Induced Anti-Ad Immune Responses .................... 194
7.4.1 Innate Immune Responses ................................................................ 195 7.4.2 T-Cell Responses .............................................................................. 195 7.4.3 Neutralizing Antibodies ................................................................... 195 7.4.4 Comparison to Other Vaccine Platforms .......................................... 195
7.5 Evading Immune Responses against Ad Vectors ......................................... 196 7.5.1 HD-Ad Vectors to Evade Vector-Specific T-Cell Responses ........... 196
Adenoviruses (Ads) are arguably one of the most potent vectors for in vivo gene delivery. They are also thought to be one of the most immunogenic vectors driving potent cellular and humoral immune responses. While this immunogenicity can be a handicap in using Ads for gene therapy, this feature can be a potent strength when Ads are instead used as gene-based vaccine. This chapter discussed this application area for Ad vectors.
