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连续接种部位转移接种提高了编码 SARS-CoV-2 S 蛋白的 DNA 疫苗诱导的 T 细胞反应。

Successive Site Translocating Inoculation Improved T Cell Responses Elicited by a DNA Vaccine Encoding SARS-CoV-2 S Protein.

机构信息

Department of Medical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Infectious Disease, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Front Immunol. 2022 Apr 19;13:875236. doi: 10.3389/fimmu.2022.875236. eCollection 2022.

Abstract

A variety of methods have been explored to increase delivery efficiencies for DNA vaccine. However, the immunogenicity of DNA vaccines has not been satisfactorily improved. Unlike most of the previous attempts, we provided evidence suggesting that changing the injection site successively (successively site-translocated inoculation, SSTI) could significantly enhance the immunogenicity of DNA vaccines in a previous study. To simplify the strategy and to evaluate its impact on candidate SARS-CoV-2 vaccines, we immunized mice with either a SARS-CoV-2 spike-based DNA vaccine or a spike protein subunit vaccine three different inoculation strategies. Our data demonstrated that S protein specific antibody responses elicited by the DNA vaccine or the protein subunit vaccine showed no significant difference among different inoculation strategies. Of interest, compared with the conventional site fixed inoculation (SFI), both successive site-translocating inoculation (SSTI) and the simplified translocating inoculation (STI) strategy improved specific T cell responses elicited by the DNA vaccine. More specifically, the SSTI strategy significantly improved both the monofunctional (IFN-γIL-2TNF-αCD8) and the multifunctional (IFN-γIL-2TNF-αCD8, IFN-γIL-2TNF-αCD4, IFN-γIL-2TNF-αCD4) T cell responses, while the simplified translocating inoculation (STI) strategy significantly improved the multifunctional CD8 (IFN-γIL-2TNF-αCD8, IFN-γIL-2TNF-αCD8) and CD4 (IFN-γIL-2TNF-αCD4, IFN-γIL-2TNF-αCD4) T cell responses. The current study confirmed that changing the site of intra muscular injection can significantly improve the immunogenicity of DNA vaccines.

摘要

已经探索了多种方法来提高 DNA 疫苗的递送效率。然而,DNA 疫苗的免疫原性尚未得到令人满意的改善。与之前的大多数尝试不同,我们提供的证据表明,在之前的研究中,连续改变注射部位(连续部位转移接种,SSTI)可以显著提高 DNA 疫苗的免疫原性。为了简化该策略并评估其对候选 SARS-CoV-2 疫苗的影响,我们使用基于 SARS-CoV-2 刺突蛋白的 DNA 疫苗或刺突蛋白亚单位疫苗,通过三种不同的接种策略对小鼠进行免疫接种。我们的数据表明,DNA 疫苗或蛋白亚单位疫苗引起的 S 蛋白特异性抗体反应在不同的接种策略之间没有显著差异。有趣的是,与常规的固定部位接种(SFI)相比,连续部位转移接种(SSTI)和简化的转移接种(STI)策略均改善了 DNA 疫苗引起的特异性 T 细胞反应。更具体地说,SSTI 策略显著改善了 DNA 疫苗引起的多功能(IFN-γIL-2TNF-αCD8)和多功能(IFN-γIL-2TNF-αCD8、IFN-γIL-2TNF-αCD4、IFN-γIL-2TNF-αCD4)T 细胞反应,而简化的转移接种(STI)策略显著改善了多功能 CD8(IFN-γIL-2TNF-αCD8、IFN-γIL-2TNF-αCD8)和 CD4(IFN-γIL-2TNF-αCD4、IFN-γIL-2TNF-αCD4)T 细胞反应。本研究证实,改变肌肉内注射部位可显著提高 DNA 疫苗的免疫原性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0622/9062103/cb03c6859948/fimmu-13-875236-g001.jpg

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