Adjuvanted, antigen loaded N-trimethyl chitosan nanoparticles for nasal and intradermal vaccination: Adjuvant- and site-dependent immunogenicity in mice
Adjuvanted, antigen loaded N-trimethyl chitosan nanoparticles for nasal and intradermal vaccination: Adjuvant- and site-dependent immunogenicity in mice
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DOI：
10.1016/j.ejps.2011.10.003
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发表时间：
2012-03-12
影响因子：
4.6
通讯作者：
Jiskoot, Wim
中科院分区：
文献类型：
--
作者：
Bal, Suzanne M.;Slutter, Bram;Jiskoot, Wim
N-三甲基壳聚糖(TMC)纳米粒经鼻腔和皮内给药后，可增强亚单位抗原的免疫原性。这项工作描述了第二代以卵清蛋白为模式抗原的TMC纳米颗粒(TMC/OVA纳米颗粒)和免疫增强剂(TMC/OVA/免疫增强剂纳米颗粒)。免疫增强剂包括Toll样受体(TLR)配体、脂多糖(LPS)、PAM(3)、CSK(4)(PAM)、CpG DNA、Nod样受体2配体胞浆二肽(MDP)和GM1神经节苷脂受体配体(CTB)。对TMC/OVA/免疫增强剂纳米粒进行了物理化学表征，并通过测定血清中的免疫球蛋白来评价其免疫原性。皮内和鼻腔免疫小鼠后，鼻腔冲洗液中的IgG1、1gG2a滴度和分泌型IgA水平明显高于未加佐剂的TMC/OVA纳米粒，而含CTB、PAM和CpG的TMC/OVA纳米粒不能诱导小鼠产生更高的免疫球蛋白、IgG1和SIgA水平。经皮内免疫后，TMC/OVA/CpG和TMC/OVA/LPS纳米粒子的免疫球蛋白滴度均高于普通TMC/OVA粒子，说明将TMC/OVA/CpG和TMC/OVA/LPS纳米粒子共包裹免疫增强剂可进一步提高疫苗的免疫原性。然而，反应的强度和质量取决于免疫增强剂和给药途径。(C)2011爱思唯尔B.V.保留所有权利。
N-trimethyl chitosan (TMC) nanoparticles have been shown to increase the immunogenicity of subunit antigens after nasal and intradermal administration. This work describes a second generation of TMC nanoparticles containing ovalbumin as a model antigen (TMC/OVA nanoparticles) and an immunopotentiator (TMC/OVA/immunopotentiator nanoparticles). The selection of immunopotentiators included Toll-like receptor (TLR) ligands lipopolysaccharide (LPS), PAM(3)CSK(4) (PAM), CpG DNA, the NOD-like receptor 2 ligand muramyl dipeptide (MDP) and the GM1 ganglioside receptor ligand, cholera toxin B subunit (CTB). The TMC/OVA/immunopotentiator nanoparticles were characterised physico-chemically and their immunogenicity was assessed by determining the serum IgG. IgG1,1gG2a titres and secretory IgA levels in nasal washes after intradermal and nasal vaccination in mice.After nasal vaccination, TMC/OVA nanoparticles containing LPS or MDP elicited higher IgG, IgG1 and sIgA levels than non-adjuvanted TMC/OVA particles, whereas nanoparticles containing CTB, PAM or CpG did not. After intradermal vaccination, the TMC/OVA/CpG and TMC/OVA/LPS nanoparticles provoked higher IgG titres than plain TMC/OVA particles.Altogether, our results show that co-encapsulation of an additional immunopotentiator with the antigen into TMC nanoparticles can further improve the immunogenicity of the vaccine. However, the strength and quality of the response depends on the immunopotentiator as well as the route of administration. (C) 2011 Elsevier B.V. All rights reserved.