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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?.

Authors :
Fausther-Bovendo H
Kobinger GP
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.

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