Abstract
Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.
Original language | English (US) |
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Pages (from-to) | 2875-2884 |
Number of pages | 10 |
Journal | Human Vaccines and Immunotherapeutics |
Volume | 10 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2014 |
Externally published | Yes |
Keywords
- Adenovirus vectors
- Cellular responses
- Humoral responses
- Innate immunity
- Pre-existing immunity
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology