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Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, what's important?.
Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, what's important?.
- Source :
-
Human vaccines & immunotherapeutics [Hum Vaccin Immunother] 2014; Vol. 10 (10), pp. 2875-84. - Publication Year :
- 2014
-
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.
- Subjects :
- Adenovirus Infections, Human immunology
Humans
Immunity, Cellular immunology
Immunity, Humoral immunology
Immunity, Innate immunology
Interferon Type I immunology
Killer Cells, Natural
T-Lymphocytes immunology
Adenovirus Infections, Human prevention & control
Adenoviruses, Human immunology
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
Immunization methods
Subjects
Details
- Language :
- English
- ISSN :
- 2164-554X
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Human vaccines & immunotherapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 25483662
- Full Text :
- https://doi.org/10.4161/hv.29594