title: Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis.
abstract: Vaccines that drive robust T-cell immunity against Mycobacterium tuberculosis (Mtb) are needed both for prophylactic and therapeutic purposes. We have recently developed a synthetic vaccine delivery platform with Pluronic-stabilized polypropylene sulfide nanoparticles (NPs), which target lymphoid tissues by their small size (∼ 30 nm) and which activate the complement cascade by their surface chemistry. Here we conjugated the tuberculosis antigen Ag85B to the NPs (NP-Ag85B) and compared their efficacy in eliciting relevant immune responses in mice after intradermal or pulmonary administration. Pulmonary administration of NP-Ag85B with the adjuvant CpG led to enhanced induction of antigen-specific polyfunctional Th1 responses in the spleen, the lung and lung-draining lymph nodes as compared to soluble Ag85B with CpG and to the intradermally-delivered formulations. Mucosal and systemic Th17 responses were also observed with this adjuvanted NP formulation and vaccination route, especially in the lung. We then evaluated protection induced by the adjuvanted NP formulation following a Mtb aerosol challenge and found that vaccination with NP-Ag85B and CpG via the pulmonary route displayed a substantial reduction of the lung bacterial burden, both compared to soluble Ag85B with CpG and to the corresponding intradermally delivered formulations. These findings highlight the potential of administrating NP-based formulations by the pulmonary route for TB vaccination.
authors.affiliation: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Ballester
authors.forename: Chiara
authors.initials: C
authors.lastname: Nembrini
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhar
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Titta
authors.forename: Cyntia
authors.initials: C
authors.lastname: de Piano
authors.forename: Miriella
authors.initials: M
authors.lastname: Pasquier
authors.forename: Eleonora
authors.initials: E
authors.lastname: Simeoni
authors.forename: André J
authors.initials: AJ
authors.lastname: van der Vlies
authors.forename: John D
authors.initials: JD
authors.lastname: McKinney
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011126:Polypropylenes / Q000737:chemistry; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018796:Immunoconjugates; D011126:Polypropylenes; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D003165:Complement System Proteins; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis