Construction and evaluation of glycoprotein-based nucleic acid vaccines for Marburg virus.

IF 5.5 3区 医学 Q1 IMMUNOLOGY Medical Microbiology and Immunology Pub Date : 2024-11-28 DOI:10.1007/s00430-024-00811-1
Xiyang Zhang, Yubo Sun, Jiaxing Zhang, Junqi Zhang, Jing Wang, Chenchen Hu, Yueyue Wang, Feiming Hu, Sirui Cai, Yuanli He, Yang Liu, Yuanjie Sun, Shuya Yang, Dongbo Jiang, Kun Yang
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Abstract

Marburg virus (MARV) is a zoonotic virus that can infect humans and non-human primates (NHPs) and lead to a fatal Marburg hemorrhagic fever (MHF), while there is no approved vaccine or antiviral treatment for MHF. The nucleic acid vaccine has unique advantages, including fast and simple preparation, easy to follow the virus mutation situation, and less adverse reactions. Therefore, we constructed the DNA and mRNA candidate vaccines based on codon-optimized MARV glycoprotein sequence, and evaluated the immune effect in mice through ELISA, ELISpot, and Flow cytometry. After the second booster immunization, both of the candidate vaccines induced strong humoral immune response, enhanced T cell response, and elicited neutralizing antibodies. Notably, DNA candidate vaccine induced stronger humoral immune response, while mRNA candidate vaccine elicited higher levels of IFN-γ and IL-4. In addition, transcriptome analysis revealed that the candidate vaccines activated immune response related pathways. Our study shed new light on the nucleic acid vaccines for MARV and further confirmed the potential of nucleic acid vaccine for future MHF prevention and control.

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构建和评估基于糖蛋白的马尔堡病毒核酸疫苗。
马尔堡病毒(MARV)是一种人畜共患病毒,可感染人类和非人灵长类动物(NHPs),并导致致命的马尔堡出血热(MHF),而目前尚无针对马尔堡出血热的获批疫苗或抗病毒治疗方法。核酸疫苗具有制备简单快捷、易于跟踪病毒变异情况、不良反应少等独特优势。因此,我们根据经过密码子优化的MARV糖蛋白序列构建了DNA和mRNA候选疫苗,并通过ELISA、ELISpot和流式细胞术评估了小鼠的免疫效果。在第二次加强免疫后,两种候选疫苗都诱导了强烈的体液免疫反应,增强了T细胞反应,并激发了中和抗体。值得注意的是,DNA 候选疫苗诱导了更强的体液免疫反应,而 mRNA 候选疫苗则诱导了更高水平的 IFN-γ 和 IL-4。此外,转录组分析表明,候选疫苗激活了与免疫应答相关的通路。我们的研究为MARV核酸疫苗提供了新的思路,并进一步证实了核酸疫苗在未来MHF防控中的潜力。
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来源期刊
CiteScore
10.60
自引率
0.00%
发文量
29
审稿时长
1 months
期刊介绍: Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.
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