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DNA 启动免疫增强重组 LcrV 蛋白疫苗引发的鼠疫耶尔森菌 LcrV 特异性 B 细胞反应的初步研究

Pilot Study on the Use of DNA Priming Immunization to Enhance Y. pestis LcrV-Specific B Cell Responses Elicited by a Recombinant LcrV Protein Vaccine.

作者信息

Li Wei, Wang Shixia, Lu Shan

机构信息

Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

出版信息

Vaccines (Basel). 2013 Dec 27;2(1):36-48. doi: 10.3390/vaccines2010036.

Abstract

Recent studies indicate that DNA immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. However, there is limited information on the mechanism of this effect. In particular, it is not known whether DNA immunization can also enhance the development of antigen-specific B cell development. In this report, a pilot study was conducted using plague LcrV immunogen as a model system to determine whether DNA immunization is able to enhance LcrV-specific B cell development in mice. Plague is an acute and often fatal infectious disease caused by Yersinia pestis (Y. pestis). Humoral immune responses provide critical protective immunity against plague. Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge. In the current study, we further evaluated whether the use of a DNA priming immunization is able to enhance the immunogenicity of a recombinant LcrV protein vaccine, and in particular, the development of LcrV-specific B cells. Our data indicate that DNA immunization was able to elicit high-level LcrV antibody responses when used alone or as part of a prime-boost immunization approach. Most significantly, DNA immunization was also able to increase the levels of LcrV-specific B cell development. The finding that DNA immunization can enhance antigen-specific B cell responses is highly significant and will help guide similar studies in other model antigen systems.

摘要

近期研究表明,在动物和人体研究中,DNA免疫在引发抗原特异性抗体反应方面效果显著。然而,关于这种效应的机制,相关信息有限。特别是,尚不清楚DNA免疫是否也能促进抗原特异性B细胞的发育。在本报告中,我们以鼠疫LcrV免疫原为模型系统进行了一项初步研究,以确定DNA免疫是否能够增强小鼠体内LcrV特异性B细胞的发育。鼠疫是由鼠疫耶尔森菌(Y. pestis)引起的一种急性且往往致命的传染病。体液免疫反应为抵抗鼠疫提供关键的保护性免疫。此前,我们证明表达LcrV抗原的DNA疫苗可保护小鼠免受致命的黏膜攻击。在当前研究中,我们进一步评估了采用DNA初免免疫是否能够增强重组LcrV蛋白疫苗的免疫原性,尤其是LcrV特异性B细胞的发育。我们的数据表明,DNA免疫单独使用或作为初免-加强免疫方法的一部分时,均能够引发高水平的LcrV抗体反应。最为重要的是,DNA免疫还能够提高LcrV特异性B细胞的发育水平。DNA免疫可增强抗原特异性B细胞反应这一发现具有高度重要性,将有助于指导其他模型抗原系统中的类似研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df0c/4494201/edccfbbe3a0c/vaccines-02-00036-g001.jpg

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