Pre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what's important?

Research output: Contribution to journalReview articlepeer-review

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 languageEnglish (US)
Pages (from-to)2875-2884
Number of pages10
JournalHuman Vaccines and Immunotherapeutics
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Keywords

  • Adenovirus vectors
  • Cellular responses
  • Humoral responses
  • Innate immunity
  • Pre-existing immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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