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携带全裂解物抗原的鞘磷脂脂质体在BALB/c小鼠中诱导强烈的Th2免疫反应。

Sphingomyelin liposome bearing whole lysate antigens induce strong Th2 immune response in BALB/c mice.

作者信息

Biari Nazanin, Alavizadeh Seyedeh Hoda, Chavoshian Omid, Abbasi Azam, Saberi Zahra, Jalali Seyed Amir, Khamesipoure Ali, Jaafari Mahmoud Reza, Badiee Ali

机构信息

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Iran J Basic Med Sci. 2021 Feb;24(2):222-231. doi: 10.22038/IJBMS.2020.50471.11496.

Abstract

OBJECTIVES

Whole lysate antigens (WLL) has been shown to be effective to tackle leishmaniasis in murine models. Although liposomes can be considered as promising vaccines, the activity of phospholipase-A (PLA) in WLL, breeds difficulties to preparing stable liposomal WLL. One strategy to overcome this shortcoming is to use lipids such as sphingomyelin (SM) which is resistant against PLA. This study aim is formulating stable SM liposomes containing WLL and comparing their adjuvant effects with another first generation vaccine , i.e. solube Antigen (SLA) liposomes in BALB/c mice.

MATERIALS AND METHODS

BALB/c mice were immunized subcutaneously, three times with 2-week intervals, with Empty-liposome (E-lipo), Particulate WLL, Liposome-WLL, Liposome-SLA and control Buffer, three times every 2-week. Protection was assessed through measuring the swollen footpads and the load of parasites in the spleen. Other factors were used to assess the response of immune system by means of IgG subclasses, IL-4 and IFN-γ levels and intracellular cytokine assay in cultured splenocytes.

RESULTS

Although liposomal WLL were stable in terms of physicochemical properties, mice received Liposome-WLL did not reduce footpad swelling. The load of parasites in spleen and levels of IL-4- were also higher compared to other immunized groups. In terms of IgG isotypes, no considerable difference observed in mice received Liposome-WLL or other formulations.

CONCLUSION

Liposome-WLL could be a suitable vaccine delivery system when a Th2 response is desired. Also, further studies are warranted to fully understand the role of sphingomyelin in inducing an immune response.

摘要

目的

全裂解物抗原(WLL)已被证明在小鼠模型中对治疗利什曼病有效。尽管脂质体可被视为有前景的疫苗,但WLL中磷脂酶A(PLA)的活性给制备稳定的脂质体WLL带来了困难。克服这一缺点的一种策略是使用对PLA有抗性的脂质,如鞘磷脂(SM)。本研究旨在制备含WLL的稳定SM脂质体,并在BALB/c小鼠中比较它们与另一种第一代疫苗即可溶性抗原(SLA)脂质体的佐剂效果。

材料与方法

将BALB/c小鼠皮下免疫,每隔2周免疫3次,分别用空脂质体(E-lipo)、颗粒状WLL、脂质体-WLL、脂质体-SLA和对照缓冲液,每2周免疫3次。通过测量足垫肿胀和脾脏中的寄生虫负荷来评估保护作用。还通过IgG亚类、IL-4和IFN-γ水平以及培养的脾细胞中的细胞内细胞因子测定来评估免疫系统的反应。

结果

尽管脂质体WLL在物理化学性质方面是稳定的,但接受脂质体-WLL的小鼠并未减轻足垫肿胀。与其他免疫组相比,脾脏中的寄生虫负荷和IL-4水平也更高。就IgG同种型而言,接受脂质体-WLL或其他制剂的小鼠中未观察到显著差异。

结论

当需要Th2反应时,脂质体-WLL可能是一种合适的疫苗递送系统。此外,有必要进行进一步研究以充分了解鞘磷脂在诱导免疫反应中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b01/8061322/2aef19919a20/IJBMS-24-222-g001.jpg

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