Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
21
05
2019
accepted:
01
11
2019
revised:
30
12
2019
pubmed:
17
12
2019
medline:
29
2
2020
entrez:
17
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31841560
doi: 10.1371/journal.ppat.1008180
pii: PPATHOGENS-D-19-00912
pmc: PMC6936886
doi:
Substances chimiques
DEFA5 protein, human
0
alpha-Defensins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008180Subventions
Organisme : NIAID NIH HHS
ID : U19 AI096040
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI128751
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI124377
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126603
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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