title: Rational design of pathogen-mimicking amphiphilic materials as nanoadjuvants.
abstract: An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The value of using polyanhydride nanovaccines was demonstrated by the induction of long-lived protection against a lethal challenge of Yersinia pestis following a single administration ten months earlier. This approach has the tantalizing potential to catalyze the development of next generation vaccines against diseases caused by emerging and re-emerging pathogens.
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
authors.forename: Bret D
authors.initials: BD
authors.lastname: Ulery
authors.forename: Latrisha K
authors.initials: LK
authors.lastname: Petersen
authors.forename: Yashdeep
authors.initials: Y
authors.lastname: Phanse
authors.forename: Chang Sun
authors.initials: CS
authors.lastname: Kong
authors.forename: Scott R
authors.initials: SR
authors.lastname: Broderick
authors.forename: Devender
authors.initials: D
authors.lastname: Kumar
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.forename: Brenda
authors.initials: B
authors.lastname: Carrillo-Conde
authors.forename: Krishna
authors.initials: K
authors.lastname: Rajan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
authors.forename: Bryan H
authors.initials: BH
authors.lastname: Bellaire
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells; D015195:Drug Design; D005260:Female; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D015233:Models, Statistical; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D049388:Polyanhydrides / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry*; D015010:Yersinia pestis
chemical_list: D000276:Adjuvants, Immunologic; D049388:Polyanhydrides; D014612:Vaccines