title: PPS nanoparticles as versatile delivery system to induce systemic and broad mucosal immunity after intranasal administration.
abstract: Degradable polymer nanoparticles (NPs, 50 nm) based on polypropylene sulfide (PPS) were conjugated to thiolated antigen and adjuvant proteins by reversible disulfide bonds and evaluated in mucosal vaccination. Ovalbumin was used as a model antigen, and antigen-conjugated NPs were administered intranasally in the mouse. We show penetration of nasal mucosae, transit via M cells, and uptake by antigen-presenting cells in the nasal-associated lymphoid tissue. Ovalbumin-conjugated NPs induced cytotoxic T lymphocytic responses in lung and spleen tissues, as well as humoral response in mucosal airways. Co-conjugation of the TLR5 ligand flagellin further enhanced humoral responses in the airways as well as in the distant vaginal and rectal mucosal compartments and induced cellular immune responses with a Th1 bias, in contrast with free flagellin. The PPS NP platform thus appears interesting as a platform for intranasally-administered mucosal vaccination for inducing broad mucosal immunity.
authors.affiliation: Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Armando
authors.initials: A
authors.lastname: Stano
authors.forename: André J
authors.initials: AJ
authors.lastname: van der Vlies
authors.forename: Mikael M
authors.initials: MM
authors.lastname: Martino
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: Eleonora
authors.initials: E
authors.lastname: Simeoni
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000032:analysis; D000938:Antigen-Presenting Cells / Q000276:immunology; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009297:Nasal Mucosa / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011126:Polypropylenes / Q000008:administration & dosage / Q000737:chemistry; D012007:Rectum / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014621:Vagina / Q000276:immunology
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D011126:Polypropylenes; D010047:Ovalbumin