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基于脂质体的鼻内递送达玛烷型脂肽疫苗候选物用于 A 组链球菌的免疫

Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus.

机构信息

The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia.

Institute for Glycomics, Griffith University, Gold Coast 4215, Australia.

出版信息

Acta Biomater. 2016 Sep 1;41:161-8. doi: 10.1016/j.actbio.2016.04.012. Epub 2016 Apr 7.

Abstract

UNLABELLED

Group A streptococcus (GAS), an exclusively human pathogen, causes a wide range of diseases ranging from trivial to life threatening. Treatment of infection is often ineffective following entry of bacteria into the bloodstream. To date, there is no vaccine available against GAS. In this study, cationic liposomes encapsulating lipopeptide-based vaccine candidates against GAS have been employed for intranasal vaccine delivery. Cationic liposomes were prepared with dimethyldioctadecylammonium bromide (DDAB) using the film hydration method. Female Swiss mice were immunized intranasally with the liposomes. In contrast to unmodified peptides, lipopeptides entrapped by liposomes induced both mucosal and systemic immunity, IgA and IgG (IgG1 and IgG2a) production in mice, respectively. High levels of antibody (IgA and IgG) titres were detected even five months post immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines.

STATEMENT OF SIGNIFICANCE

Group A streptococcus, causing rheumatic heart diseases, kills approximately half a million people annually. There is no vaccine available against the infection. Mucosal immunity is vital in ensuring an individual is protected as this gram positive bacteria initially colonizes at the throat. Herein, we demonstrated that lipopeptides entrapped by liposomes induced both mucosal and systemic immunity. High levels of antibody (IgA and IgG) titres were detected even five months post immunization and lead vaccine candidate was able to induce humoral immune responses even after single immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines.

摘要

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A 组链球菌(GAS),一种专性人类病原体,可引起从轻微到危及生命的各种疾病。细菌进入血液后,感染的治疗往往效果不佳。迄今为止,尚无针对 GAS 的疫苗。在这项研究中,已将包封针对 GAS 的基于脂肽的疫苗候选物的阳离子脂质体用于鼻内疫苗递送。阳离子脂质体是使用薄膜水化法用二甲基双十八烷基溴化铵(DDAB)制备的。雌性瑞士小鼠通过鼻内免疫用脂质体免疫。与未修饰的肽相比,包封在脂质体中的脂肽分别诱导了粘膜和全身免疫,在小鼠中产生了 IgA 和 IgG(IgG1 和 IgG2a)。即使在免疫后五个月,也检测到了高水平的抗体(IgA 和 IgG)效价。因此,脂肽和脂质体的组合为鼻内疫苗提供了一种非常有前途的递送系统。

意义声明

导致风湿性心脏病的 A 组链球菌每年导致约 50 万人死亡。针对这种感染尚无疫苗。粘膜免疫对于确保个体受到保护至关重要,因为这种革兰氏阳性细菌最初会在喉咙中定植。在此,我们证明了包封在脂质体中的脂肽诱导了粘膜和全身免疫。即使在免疫后五个月,也检测到了高水平的抗体(IgA 和 IgG)效价,并且即使在单次免疫后,先导疫苗候选物也能够诱导体液免疫应答。因此,脂肽和脂质体的组合为鼻内疫苗提供了一种非常有前途的递送系统。

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