Prevention of influenza virus infection and transmission by intranasal administration of a porous maltodextrin nanoparticle-formulated vaccine

Int J Pharm. 2020 May 30:582:119348. doi: 10.1016/j.ijpharm.2020.119348. Epub 2020 Apr 20.

Abstract

Influenza vaccines administered intramuscularly exhibit poor mucosal immune responses in the respiratory tract which is the prime site of the infection. Intranasal vaccination is a potential route for vaccine delivery which has been demonstrated effective in inducing protective immune responses in both systemic and mucosal compartments. For this purpose, nanoparticles have been used as antigen delivery systems to improve antigen capture by immune cells. In this paper we demonstrate efficient delivery of viral antigens to airway epithelial cells, macrophages and dendritic cells, using polysaccharide nanoparticles (NPL), leading to a strong protection against influenza virus infection. A formulation combining split Udorn virus antigens with NPL and the mucosal protein adjuvant CTA1-DD was administered intranasally and resulted in an enhanced specific humoral immune response. Furthermore, NPL carrying split Udorn, with or without CTA1-DD, inhibited virus transmission from infected to uninfected naive mice. These results demonstrate that an intranasal delivery system combining NPL, mucosal adjuvant CTA1-DD and split virus antigens confers robust protection against influenza infection and inhibits virus transmission.

Keywords: CTA1-DD; Influenza; Intranasal; Nanoparticle; Vaccine.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood
  • Antigens, Viral / administration & dosage*
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • Cholera Toxin / administration & dosage*
  • Cholera Toxin / chemistry
  • Cholera Toxin / immunology
  • Disease Models, Animal
  • Drug Carriers*
  • Drug Compounding
  • Immunity, Humoral / drug effects
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Nanoparticles*
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / transmission
  • Orthomyxoviridae Infections / virology
  • Polysaccharides / chemistry*
  • Porosity
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Antigens, Viral
  • CTA1-DD protein, recombinant
  • Drug Carriers
  • Influenza Vaccines
  • Polysaccharides
  • Recombinant Fusion Proteins
  • maltodextrin
  • Cholera Toxin