INSERM, UMR U1152, Laboratoire d'Excellence Inflamex, Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodeling), Université Paris Diderot, Sorbonne Paris Cité, 75018, Paris, France.
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.
Biomaterials. 2019 Oct;217:119308. doi: 10.1016/j.biomaterials.2019.119308. Epub 2019 Jun 26.
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.
由于不理想的疫苗接种方案（例如，通过肌内注射给予的灭活病毒），目前大多数流感病毒疫苗未能在肺部黏膜（病毒进入部位）产生强大的免疫力。通过使用含有适当佐剂的局部递送疫苗，可以改善黏膜免疫。在这里，我们在小鼠模型中显示，在灭活流感疫苗中加入银纳米颗粒（AgNPs）可降低病毒载量并预防流感感染后过度的肺部炎症。同时，AgNPs 增强了特异性 IgA 分泌浆细胞和抗体滴度，这是成功的黏膜免疫的标志。此外，在存在 AgNPs 的情况下进行疫苗接种而不是使用金纳米颗粒，可保护小鼠免受致命流感的侵害。与其他商业佐剂（角鲨烯/油基乳剂）或银盐相比，AgNPs 通过促进支气管相关淋巴组织（BALT）新生，以较低的毒性刺激更强的抗原特异性 IgA 产生，并作为一种真正的黏膜佐剂。
