Induction of mucosal immunity by pulmonary administration of a cell-targeting nanoparticle

Drug Deliv. 2021 Dec;28(1):1585-1593. doi: 10.1080/10717544.2021.1955040.

Abstract

We previously found that a nanoparticle constructed with an antigen, benzalkonium chloride (BK) and γ-polyglutamic acid (γ-PGA) showed high Th1 and Th2-type immune induction after subcutaneous administration. For prophylaxis of respiratory infections, however, mucosal immunity should be induced. In this study, we investigated the effect of pulmonary administration of a nanoparticle comprising ovalbumin (OVA) as a model antigen, BK, and γ-PGA on induction of mucosal immunity in the lungs and serum. The complex was strongly taken up by RAW264.7 and DC2.4cells. After pulmonary administration, lung retention was longer for the OVA/BK/γ-PGA complex than for OVA alone. OVA-specific serum immunoglobulin (Ig)G was highly induced by the complex. High IgG and IgA levels were also induced in the bronchoalveolar lavage fluid, and in vivo toxicities were not observed. In conclusion, we effectively and safely induced mucosal immunity by pulmonary administration of an OVA/BK/γ-PGA complex.

Keywords: Vaccine; mucosal immunity; nanoparticles; pulmonary administration; γ-polyglutamic acid.

MeSH terms

  • Animals
  • Benzalkonium Compounds / administration & dosage
  • Benzalkonium Compounds / pharmacology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Immunity, Mucosal / drug effects*
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin G / drug effects
  • Lung / drug effects*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Ovalbumin / administration & dosage
  • Ovalbumin / pharmacology*
  • Polyglutamic Acid / administration & dosage
  • Polyglutamic Acid / pharmacology*
  • RAW 264.7 Cells
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Benzalkonium Compounds
  • Immunoglobulin A
  • Immunoglobulin G
  • Polyglutamic Acid
  • Ovalbumin

Grants and funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI under grants [JP20K12649 and JP20K07156].