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肽疫苗接种优于使用重组噬菌体 λ 亚单位疫苗的基因疫苗接种。

Peptide vaccination is superior to genetic vaccination using a recombineered bacteriophage λ subunit vaccine.

机构信息

Southern Alberta Cancer Research Institute, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, AB, Canada.

出版信息

Vaccine. 2012 Feb 1;30(6):998-1008. doi: 10.1016/j.vaccine.2011.12.070. Epub 2011 Dec 28.

Abstract

Genetic immunization holds promise as a vaccination method, but has so far proven ineffective in large primate and human trials. Herein, we examined the relative merits of genetic immunization and peptide immunization using bacteriophage λ. Bacteriophage λ has proven effective in immune challenge models using both immunization methods, but there has never been a direct comparison of efficacy and of the quality of immune response. In the current study, this vector was produced using a combination of cis and trans phage display. When antibody titers were measured from immunized animals together with IL-2, IL-4 and IFNγ production from splenocytes in vitro, we found that proteins displayed on λ were superior at eliciting an immune response in comparison to genetic immunization with λ. We also found that the antibodies produced in response to immunization with λ displayed proteins bound more epitopes than those produced in response to genetic immunization. Finally, the general immune response to λ inoculation, whether peptide or genetic, was dominated by a Th1 response, as determined by IFNγ and IL-4 concentration, or by a higher concentration of IgG2a antibodies.

摘要

基因免疫作为一种疫苗接种方法具有很大的应用前景,但迄今为止,在大型灵长类动物和人体试验中证明其效果不佳。在此,我们利用噬菌体λ来研究基因免疫和肽免疫的相对优势。噬菌体λ已被证明在两种免疫方法的免疫挑战模型中都非常有效,但从来没有对其疗效和免疫反应质量进行过直接比较。在本研究中,该载体是通过顺式和反式噬菌体展示相结合的方法产生的。当我们从免疫动物中测量抗体滴度,以及体外脾细胞产生的 IL-2、IL-4 和 IFNγ时,我们发现与基因免疫相比,λ展示的蛋白能更好地引发免疫反应。我们还发现,针对λ免疫接种产生的抗体比针对基因免疫产生的抗体能结合更多的表位。最后,无论是肽免疫还是基因免疫,λ接种引起的一般免疫反应主要是 Th1 反应,这是通过 IFNγ和 IL-4 的浓度或 IgG2a 抗体浓度较高来确定的。

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