Therapeutic potential of adenovirus-mediated delivery of β-defensin 2 for experimental otitis media.
Otitis media (OM), one of the most prevalent diseases in young children, is clinically important owing to its high incidence in children and its potential impact on language development and motor coordination. OM is the most common reason for the prescription of antibiotics (accounting for 25% of prescriptions) due to its extremely high incidence. A recent increase in antibiotic resistance among OM pathogens is emerging as a major public health concern globally, which led us to consider non-antibiotic approaches for the management of OM. In this study, we evaluated gene transfer of an antimicrobial peptide, human β-defensin 2 (DEFB4), using an adenoviral vector (Ad5 with deletions of E1/E3/E4) as a potential therapeutic approach. We demonstrated that the transduction of human β-defensin 2 induces the production of human β-defensin 2 and suppresses non-typeable Haemophilus influenzae (NTHi) adhesion to human middle ear epithelial cells. Moreover, intratympanic inoculation of Ad-DEFB4 was found to attenuate NTHi-induced middle ear effusions without eliciting a significant immune response. Most importantly, intratympanic inoculation of Ad-DEFB4 appeared to significantly augment clearance of NTHi from middle ear cavity. Collectively, our results suggest that intratympanic gene delivery of antimicrobial molecules may serve as an alternative/adjuvant approach for the management of OM.
Department of Head and Neck Surgery, University of California, Los Angeles, CA, USA.
Jeong-Im
JI
Woo
Department of Head and Neck Surgery, University of California, Los Angeles, CA, USA.
Sung-Hee
SH
Kil
GenVec Inc., Rockville, MD, USA.
Douglas E
DE
Brough
Department of Head and Neck Surgery, University of California, Los Angeles, CA, USA.
Yoo Jin
YJ
Lee
Department of Head and Neck Surgery, University of California, Los Angeles, CA, USA.
David J
DJ
Lim
Department of Head and Neck Surgery, University of California, Los Angeles, CA, USA skmoon@mednet.ucla.edu djlim@mednet.ucla.edu.
Sung K
SK
Moon
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D058491:Bacterial Load / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D004432:Ear, Middle / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006192:Haemophilus Infections / Q000150:complications / Q000628:therapy*; D006193:Haemophilus influenzae / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010033:Otitis Media / Q000209:etiology / Q000517:prevention & control*; D017384:Sequence Deletion / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D023083:beta-Defensins / Q000008:administration & dosage* / Q000235:genetics
C106641:DEFB4A protein, human; D023083:beta-Defensins
Middle ear; defensin; gene delivery; non-typeable Haemophilus influenzae; otitis media