Pre-existing immunity against Ad vectors
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2014
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| _version_ | 1866901360131178496 |
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| author | Fausther-Bovendo, Hugues Kobinger, Gary P |
| author_facet | Fausther-Bovendo, Hugues Kobinger, Gary P |
| contents | (Uploaded by Plazi for the Bat Literature Project) 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. |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_13533684 |
| institution | Zenodo |
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| publishDate | 2014 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Pre-existing immunity against Ad vectors Fausther-Bovendo, Hugues Kobinger, Gary P Biodiversity Mammalia Chiroptera Chordata Animalia bats bat (Uploaded by Plazi for the Bat Literature Project) 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. |
| title | Pre-existing immunity against Ad vectors |
| topic | Biodiversity Mammalia Chiroptera Chordata Animalia bats bat |
| url | https://doi.org/10.5281/zenodo.13533684 |