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

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

Author information

1
INSERM, UMR U1152, Laboratoire d'Excellence Inflamex, Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodeling), Université Paris Diderot, Sorbonne Paris Cité, 75018, Paris, France.
2
INSERM, UMR U1152, Laboratoire d'Excellence Inflamex, Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodeling), Université Paris Diderot, Sorbonne Paris Cité, 75018, Paris, France; Department of Pneumology A, AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Paris, 75018, Paris, France.
3
ImagoSeine, Electron Microscopy Facility, Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205, Cedex 13, Paris, France.
4
Department of Pathology, AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Paris, 75018, Paris, France.
5
INSERM, UMR U1152, Laboratoire d'Excellence Inflamex, Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodeling), Université Paris Diderot, Sorbonne Paris Cité, 75018, Paris, France. Electronic address: ignacio.garcia-verdugo@inserm.fr.

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

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