Silver nanoparticle-adjuvanted vaccine protects against lethal influenza infection through inducing BALT and IgA-mediated mucosal immunity

Biomaterials. 2019 Oct:217:119308. doi: 10.1016/j.biomaterials.2019.119308. Epub 2019 Jun 26.

Abstract

Most of current influenza virus vaccines fail to develop a strong immunity at lung mucosae (site of viral entry) due to sub-optimal vaccination protocols (e.g. inactivated virus administered by parenteral injections). Mucosal immunity could be improved by using locally-delivered vaccines containing appropriate adjuvants. Here we show, in a mouse model, that inclusion of silver nanoparticles (AgNPs) in virus-inactivated flu vaccine resulted in reduction of viral loads and prevention of excessive lung inflammation following influenza infection. Concomitantly, AgNPs enhanced specific IgA secreting plasma cells and antibodies titers, a hallmark of successful mucosal immunity. Moreover, vaccination in the presence of AgNPs but not with gold nanoparticles, protected mice from lethal flu. Compared with other commercial adjuvants (squalene/oil-based emulsion) or silver salts, AgNPs stimulated stronger antigen specific IgA production with lower toxicity by promoting bronchus-associated lymphoid tissue (BALT) neogenesis, and acted as a bona fide mucosal adjuvant.

Keywords: Adjuvant; Immunity; Influenza virus; Lung vaccination; Silver nanoparticles; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Bronchi / immunology
  • Dogs
  • Germinal Center / drug effects
  • Germinal Center / metabolism
  • Humans
  • Immunity, Mucosal* / drug effects
  • Immunoglobulin A / metabolism*
  • Inflammation / pathology
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / immunology*
  • Madin Darby Canine Kidney Cells
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / virology
  • Silver / chemistry*
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Immunoglobulin A
  • Influenza Vaccines
  • Silver