title: Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, what's important?.
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.
authors.affiliation: a National Microbiology Laboratory ; Public health Agency of Canada ; Winnipeg , MB Canada.
authors.forename: Hugues
authors.initials: H
authors.lastname: Fausther-Bovendo
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
mesh_terms: D000258:Adenovirus Infections, Human / Q000276:immunology / Q000517:prevention & control*; D000260:Adenoviruses, Human / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007370:Interferon Type I / Q000276:immunology; D007694:Killer Cells, Natural; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007370:Interferon Type I
keywords: Adenovirus vectors; cellular responses; humoral responses; innate immunity; pre-existing immunity