title: Design of a protective single-dose intranasal nanoparticle-based vaccine platform for respiratory infectious diseases.
abstract: Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant protein F1-V alone and MPLA-adjuvanted F1-V, the nanoparticle-based vaccination regimen induced an immune response that was characterized by high titer and high avidity IgG1 anti-F1-V antibody that persisted for at least 23 weeks post-vaccination. After challenge, no Y. pestis were recovered from the lungs, livers, or spleens of mice vaccinated with the nanoparticle-based formulation and histopathological appearance of lung, liver, and splenic tissues from these mice post-vaccination was remarkably similar to uninfected control mice.
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Bret D
authors.initials: BD
authors.lastname: Ulery
authors.forename: Devender
authors.initials: D
authors.lastname: Kumar
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D003141:Communicable Diseases / Q000276:immunology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D009928:Organ Specificity; D010930:Plague / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D049388:Polyanhydrides / Q000737:chemistry; D012995:Solubility; D014611:Vaccination; D015010:Yersinia pestis / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D010931:Plague Vaccine; D049388:Polyanhydrides