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编码yidR和IL-17的DNA疫苗联合免疫增强小鼠模型宿主对感染的免疫反应。

Co-immunization with DNA vaccines encoding yidR and IL-17 augments host immune response against infection in mouse model.

作者信息

Lv Zheng, Zhang Xuan, Zhao Kelei, Du Lianming, Wang Xinrong, Chu Yiwen, Huang Ting

机构信息

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of pharmacy, Chengdu University, Chengdu, China.

Institute for Advanced Study, Chengdu University, Chengdu, China.

出版信息

Virulence. 2024 Dec;15(1):2345019. doi: 10.1080/21505594.2024.2345019. Epub 2024 Apr 24.

Abstract

is an important gram-negative bacterium that causes severe respiratory and healthcare-associated infections. Although antibiotic therapy is applied to treat severe infections caused by , drug-resistant isolates pose a huge challenge to clinical practices owing to adverse reactions and the mismanagement of antibiotics. Several studies have attempted to develop vaccines against , but there are no licensed vaccines available for the control of infection. In the current study, we constructed a novel DNA vaccine, pVAX1-YidR, which encodes a highly conserved virulence factor YidR and a recombinant expression plasmid pVAX1-IL-17 encoding Interleukin-17 (IL-17) as a molecular adjuvant. Adaptive immune responses were assessed in immunized mice to compare the immunogenicity of the different vaccine schemes. The results showed that the targeted antigen gene was expressed in HEK293T cells using an immunofluorescence assay. Mice immunized with pVAX1-YidR elicited a high level of antibodies, induced strong cellular immune responses, and protected mice from challenge. Notably, co-immunization with pVAX1-YidR and pVAX1-IL-17 significantly augmented host adaptive immune responses and provided better protection against infections in vaccinated mice. Our study demonstrates that combined DNA vaccines and molecular adjuvants is a promising strategy to develop efficacious antibacterial vaccines against infections.

摘要

是一种重要的革兰氏阴性菌,可引起严重的呼吸道感染和医疗保健相关感染。尽管抗生素疗法用于治疗由引起的严重感染,但由于不良反应和抗生素管理不当,耐药菌株给临床实践带来了巨大挑战。几项研究试图开发针对的疫苗,但目前尚无用于控制感染的许可疫苗。在本研究中,我们构建了一种新型DNA疫苗pVAX1-YidR,其编码高度保守的毒力因子YidR,并构建了作为分子佐剂的编码白细胞介素-17(IL-17)的重组表达质粒pVAX1-IL-17。在免疫小鼠中评估适应性免疫反应,以比较不同疫苗方案的免疫原性。结果表明,使用免疫荧光法在HEK293T细胞中表达了靶向抗原基因。用pVAX1-YidR免疫的小鼠产生了高水平的抗体,诱导了强烈的细胞免疫反应,并保护小鼠免受攻击。值得注意的是,pVAX1-YidR和pVAX1-IL-17联合免疫显著增强了宿主适应性免疫反应,并为接种疫苗的小鼠提供了更好的抗感染保护。我们的研究表明,联合DNA疫苗和分子佐剂是开发针对感染的有效抗菌疫苗的一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9339/11057650/5d0d20c9cc02/KVIR_A_2345019_F0001_OC.jpg

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