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一种展示HBHA和MTP抗原的基于病毒样颗粒的疫苗在H37Ra感染的小鼠中诱导保护性免疫反应。

A VLP-Based Vaccine Displaying HBHA and MTP Antigens of Induces Protective Immune Responses in H37Ra Infected Mice.

作者信息

Wang Juan, Xie Tao, Ullah Inayat, Mi Youjun, Li Xiaoping, Gong Yang, He Pu, Liu Yuqi, Li Fei, Li Jixi, Lu Zengjun, Zhu Bingdong

机构信息

Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation, Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.

Institute of Pathogenic Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.

出版信息

Vaccines (Basel). 2023 May 4;11(5):941. doi: 10.3390/vaccines11050941.

Abstract

Heparin-binding hemagglutinin (HBHA) and pili (MTP) are important antigens on the surface of . To display these antigens effectively, the fusion protein HBHA-MTP with a molecular weight of 20 kD (L20) was inserted into the receptor-binding hemagglutinin (HA) fragment of influenza virus and was expressed along with matrix protein M1 in Sf9 insect cells to generate influenza virus-like particles (LV20 in short). The results showed that the insertion of L20 into the envelope of the influenza virus did not affect the self-assembly and morphology of LV20 VLPs. The expression of L20 was successfully verified by transmission electron microscopy. Importantly, it did not interfere with the immunogenicity reactivity of LV20 VLPs. We demonstrated that LV20 combined with the adjuvant composed of DDA and Poly I: C (DP) elicited significantly higher antigen-specific antibodies and CD4/CD8 T cell responses than PBS and BCG vaccination in mice. It suggests that the insect cell expression system is an excellent protein production system, and LV20 VLPs could be a novel tuberculosis vaccine candidate for further evaluation.

摘要

肝素结合血凝素(HBHA)和菌毛(MTP)是[具体对象]表面的重要抗原。为有效展示这些抗原,将分子量为20 kD的融合蛋白HBHA - MTP(L20)插入流感病毒的受体结合血凝素(HA)片段,并与基质蛋白M1在Sf9昆虫细胞中共同表达,以产生流感病毒样颗粒(简称LV20)。结果表明,将L20插入流感病毒包膜不影响LV20病毒样颗粒的自组装和形态。通过透射电子显微镜成功验证了L20的表达。重要的是,它不干扰LV20病毒样颗粒的免疫原性反应性。我们证明,与由二油酰磷脂酰胆碱(DDA)和聚肌苷酸:聚胞苷酸(Poly I:C,DP)组成的佐剂联合使用时,LV20在小鼠中引发的抗原特异性抗体以及CD4/CD8 T细胞反应显著高于接种PBS和卡介苗。这表明昆虫细胞表达系统是一种优良的蛋白质生产系统,LV20病毒样颗粒可能是一种有待进一步评估的新型结核病疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f77/10224509/ba17275667e2/vaccines-11-00941-g001.jpg

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