title: Transcutaneous Immunization with a Band-Aid Prevents Experimental Otitis Media in a Polymicrobial Model.
abstract: Otitis media (OM) is a common pediatric disease, and nontypeableHaemophilus influenzae(NTHI) is the predominant pathogen in chronic OM, recurrent OM, and OM associated with treatment failure. OM is also a polymicrobial disease, wherein an upper respiratory tract viral infection predisposes to ascension of NTHI from the nasopharynx, the site of colonization, to the normally sterile middle ear, resulting in disease. Using a clinically relevant viral-bacterial coinfection model of NTHI-induced OM, we performed transcutaneous immunization (TCI) via a band-aid delivery system to administer each of three promising NTHI vaccine candidates derived from bacterial adhesive proteins and biofilm mediators: recombinant soluble PilA (rsPilA), chimV4, and integration host factor. Each immunogen was admixed with the adjuvant LT(R192G/L211A), a double mutant ofEscherichia coliheat-labile enterotoxin, and assessed for relative ability to prevent the onset of experimental OM. For each cohort, the presence of circulating immunogen-specific antibody-secreting cells and serum antibody was confirmed prior to intranasal NTHI challenge. After bacterial challenge, blinded video otoscopy and tympanometry revealed a significant reduction in the proportion of animals with signs of OM compared to levels in animals receiving adjuvant only, with an overall vaccine efficacy of 64 to 77%. These data are the first to demonstrate the efficacy afforded by TCI with a band-aid vaccine delivery system in a clinically relevant polymicrobial model of OM. The simplicity of TCI with a band-aid and the significant efficacy observed here hold great promise for reducing the global burden of OM in the pediatric population.
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's and The Ohio State University College of Medicine, Columbus, Ohio, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Novotny
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's and The Ohio State University College of Medicine, Columbus, Ohio, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Goodman
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's and The Ohio State University College of Medicine, Columbus, Ohio, USA lauren.bakaletz@nationwidechildrens.org.
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Bakaletz
mesh_terms: D000158:Acoustic Impedance Tests; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000279:Administration, Cutaneous; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000235:genetics; D002682:Chinchilla; D060085:Coinfection / Q000517:prevention & control*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000008:administration & dosage* / Q000235:genetics; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D010033:Otitis Media / Q000473:pathology / Q000517:prevention & control*; D038781:Otoscopy; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D018073:Haemophilus Vaccines; C027538:heat-labile enterotoxin, E coli
keywords: IHF; biofilms; chimV4; nontypeable Haemophilus influenzae; rsPilA