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首页> 外文期刊>Antibodies >Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally
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Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

机译：鼻内给药的可溶性和纳米粒子偶联抗原的全身和粘膜抗体反应。

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Nanoparticles (NPs) are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n.) priming followed by i.n. or subcutaneous (s.c.) boosting immunization affects the humoral immune response to chicken ovalbumin (Ova) and Ova conjugated to 20 nm NPs (NP-Ova). We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA). In contrast, 100 μg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.
机译：为了开发疫苗，越来越多地将纳米颗粒（NP）以及抗原载体和免疫刺激剂用于药物递送。在这项工作中，我们研究了鼻内（i.n.）引发后i.n.的方式。或皮下（s.c.）加强免疫会影响对鸡卵清蛋白（Ova）和与20 nm NPs偶联的Ova（NP-Ova）的体液免疫反应。我们证明用20 mg可溶性Ova引发，这是已知的通过胃管给药可触发口服耐受的剂量，可诱导大量全身性IgG1和IgG2c以及粘膜抗体。在s.c.之后，这些反应进一步增强。用Ova和完全的弗氏佐剂（Ova + CFA）进行免疫。相比之下，通过NP递送的100μgOva诱导了以IgG1为主的全身反应，并引发了肠粘膜分泌IgA。继次或i.n.用Ova + CFA或NP-Ova免疫后，全身IgG1滴度显着增加，并且在经NP-Ova鼻注的小鼠中诱导了血清IgG2c和肠道抗体。仅经卵母细胞增强的Ova和NP-Ova致敏的小鼠在引发后长达6个月内表现出明显的全身和粘膜滴度，而经i.n.致敏的小鼠的抗体随时间下降。我们的结果表明，尽管NP传递的Ova量比可溶形式传递的Ova少1000倍，但在初次免疫后6个月，全身和粘膜的抗原特异性抗体反应基本相同。此外，NP-Ova引发的小鼠的i.n.和s.c.增强策略均能够诱导极化的Th1 / Th2免疫应答以及肠道抗体。然而，只有通过使用异质的初免-加强策略，才能启动持久的抗体反应。这些结果为未来粘膜疫苗的开发，以及加深我们对粘膜抗体反应的理解提供了宝贵的见识。

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