新型鼻内纳米乳剂佐剂流感疫苗在小鼠模型中的有效性、免疫原性和稳定性

Efficacy, immunogenicity and stability of a novel intranasal nanoemulsion-adjuvanted influenza vaccine in a murine model.

作者信息

Hamouda Tarek, Chepurnov Alexander, Mank Nicholas, Knowlton Jessica, Chepurnova Tatiana, Myc Andrzej, Sutcliffe Joyce, Baker James R

机构信息

NanoBio Corp, Ann Arbor, MI, USA.

出版信息

Hum Vaccin. 2010 Jul;6(7):585-94. doi: 10.4161/hv.6.7.11818.

Abstract

Mutations of influenza virus increase concerns of worldwide epidemics resulting from the newly emergent strains. Current influenza vaccines are inefficient and require annual vaccinations. W805EC adjuvant is an oil-in-water emulsion composed of nanodroplets with an average diameter of approximately 400 nm. The nanoemulsion adjuvant has been used successfully to stimulate the immune response when mixed with several other antigens in animal models. In this study, W805EC nanoemulsion adjuvant activity was evaluated using nasal influenza vaccination in a murine model. Five to twenty percent W805EC adjuvant was used to inactivate influenza A/Puerto Rico/8/34/05 (H1N1). Mice immunized with the nanoemulsion adjuvanted influenza virus intranasally showed a robust specific humoral immune response as demonstrated using ELISA and HAI assays. Serum HAI titers were more than 104 following two vaccinations. Vaccinated mice were also protected against challenge with an LD80 of live influenza virus. Splenocytes from vaccinated mice were assayed for cytokine production following virus stimulation. The cytokine profile demonstrated a robust cellular immune response with enhanced Th1 and Th17 immunity that provided balanced immunity against both intracellular and extracellular forms of the virus. Additionally, the vaccine preparations showed minimal protein degradation but remained potent when stored at 4°C for up to three months. This work demonstrates that W805EC nanoemulsion adjuvant can effectively enhance the immunogenicity of influenza hemagglutinin antigen. The nanoemulsion adjuvant can result in antigen sparing and cross-protection. The potential exists for a nasally administered influenza vaccine that may require little or no refrigerated storage.

摘要

流感病毒的变异增加了对新出现毒株引发全球疫情的担忧。目前的流感疫苗效率低下,需要每年接种。W805EC佐剂是一种水包油乳液,由平均直径约400纳米的纳米液滴组成。在动物模型中,这种纳米乳液佐剂与其他几种抗原混合使用时,已成功用于刺激免疫反应。在本研究中,使用小鼠模型通过鼻腔接种流感疫苗来评估W805EC纳米乳液佐剂的活性。用5%至20%的W805EC佐剂来灭活甲型流感病毒/波多黎各/8/34/05(H1N1)。通过酶联免疫吸附测定(ELISA)和血凝抑制试验(HAI)证明,经纳米乳液佐剂鼻内免疫的小鼠表现出强烈的特异性体液免疫反应。两次接种后,血清HAI滴度超过104。接种疫苗的小鼠也受到了保护,可抵御80%致死剂量的活流感病毒攻击。对接种疫苗小鼠的脾细胞在病毒刺激后进行细胞因子产生检测。细胞因子谱显示出强烈的细胞免疫反应,Th1和Th17免疫增强,提供了针对细胞内和细胞外形式病毒的平衡免疫。此外,疫苗制剂显示出最小程度的蛋白质降解,在4°C下储存长达三个月时仍保持效力。这项工作表明,W805EC纳米乳液佐剂可有效增强流感血凝素抗原的免疫原性。该纳米乳液佐剂可实现抗原节约和交叉保护。一种可能几乎不需要冷藏储存的鼻用流感疫苗具有潜在的应用前景。

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