Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo

Autoři: Lawrence J. Tartaglia aff001;  Alexander Badamchi-Zadeh aff001;  Peter Abbink aff001;  Eryn Blass aff001;  Malika Aid aff001;  Makda S. Gebre aff001;  Zhenfeng Li aff001;  Kevin Clyde Pastores aff001;  Sebastien Trott aff001;  Siddhant Gupte aff001;  Rafael A. Larocca aff001;  Dan H. Barouch aff001
Působiště autorů: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston Massachusetts, United States of America aff001;  Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America aff002
Vyšlo v časopise: Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008180
Kategorie: Research Article


Adenoviral vectors have shown significant promise as vaccine delivery vectors due to their ability to elicit both innate and adaptive immune responses. α-defensins are effector molecules of the innate immune response and have been shown to modulate natural infection with adenoviruses, but the majority of α-defensin-adenovirus interactions studied to date have only been analyzed in vitro. In this study, we evaluated the role of α-defensin 5 (HD5) in modulating adenovirus vaccine immunogenicity using various serotype adenovirus vectors in mice. We screened a panel of human adenoviruses including Ad5 (species C), Ad26 (species D), Ad35 (species B), Ad48 (species D) and a chimeric Ad5HVR48 for HD5 sensitivity. HD5 inhibited transgene expression from Ad5 and Ad35 but augmented transgene expression from Ad26, Ad48, and Ad5HVR48. HD5 similarly suppressed antigen-specific IgG and CD8+ T cell responses elicited by Ad5 vectors in mice, but augmented IgG and CD8+ T cell responses and innate cytokine responses elicited by Ad26 vectors in mice. Moreover, HD5 suppressed the protective efficacy of Ad5 vectors but enhanced the protective efficacy of Ad26 vectors expressing SIINFEKL against a surrogate Listeria-OVA challenge in mice. These data demonstrate that HD5 differentially modulates adenovirus vaccine delivery vectors in a species-specific manner in vivo.

Klíčová slova:

Adenoviruses – Antigens – Cytokines – Cytotoxic T cells – Enzyme-linked immunoassays – Immune response – T cells – Vaccines


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