Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis

Marie Ballester, Chiara Nembrini, Neeraj Dhar, Alexandre de Titta, Cyntia de Piano, Miriella Pasquier, Eleonora Simeoni, André J. van der Vlies, John D. McKinney, Jeffrey A. Hubbell, Melody A. Swartz

Research output: Contribution to journalArticle

80 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6959-6966
Number of pages8
JournalVaccine
Volume29
Issue number40
DOIs
StatePublished - Sep 16 2011

Keywords

  • Adjuvant
  • Administration route
  • Intradermal
  • Lung
  • T-helper cells
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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  • Cite this

    Ballester, M., Nembrini, C., Dhar, N., de Titta, A., de Piano, C., Pasquier, M., Simeoni, E., van der Vlies, A. J., McKinney, J. D., Hubbell, J. A., & Swartz, M. A. (2011). Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis. Vaccine, 29(40), 6959-6966. https://doi.org/10.1016/j.vaccine.2011.07.039