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

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.
AuthorsDaniel Sanchez-Guzman, Pierre Le Guen, Berengere Villeret, Nuria Sola, Remi Le Borgne, Alice Guyard, Alix Kemmel, Bruno Crestani, Jean-Michel Sallenave, Ignacio Garcia-Verdugo
JournalBiomaterials (Biomaterials) Vol. 217 Pg. 119308 (10 2019) ISSN: 1878-5905 [Electronic] Netherlands
PMID31279103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 Elsevier Ltd. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Immunoglobulin A
  • Influenza Vaccines
  • Silver
Topics
  • Adjuvants, Immunologic (pharmacology)
  • Animals
  • Bronchi (immunology)
  • Dogs
  • Germinal Center (drug effects, metabolism)
  • Humans
  • Immunity, Mucosal (drug effects)
  • Immunoglobulin A (metabolism)
  • Inflammation (pathology)
  • Influenza A Virus, H1N1 Subtype (drug effects, immunology)
  • Influenza Vaccines (immunology)
  • Influenza, Human (immunology)
  • Lymphoid Tissue (drug effects, immunology)
  • Madin Darby Canine Kidney Cells
  • Metal Nanoparticles (chemistry, ultrastructure)
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections (immunology, prevention & control, virology)
  • Silver (chemistry)
  • Vaccination

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