A plant-based oligomeric CD2v extracellular domain antigen exhibits equivalent immunogenicity to the live attenuated vaccine ASFV-G-∆I177L.

IF 5.5 3区 医学 Q1 IMMUNOLOGY
Giang Thu Nguyen, Thanh Thi Le, Son Duy Thai Vu, Tra Thi Nguyen, My Thi Tra Le, Van Thi Pham, Hien Thi Thu Nguyen, Thuong Thi Ho, Hang Thi Thu Hoang, Hanh Xuan Tran, Ha Hoang Chu, Ngoc Bich Pham
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Abstract

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a deadly, highly contagious disease in both domestic pigs and wild boar. With mortality up to 100%, the disease has been making a serious impact on the swine industry worldwide. Because no effective antiviral treatment has been observed, proactive prevention such as vaccination remains the key to controlling the outbreak. In the pursuit of expediting vaccine development, our current work has made the first report for heterologous production of the viral outer envelope glycoprotein CD2v extracellular domain (CD2v ED), a proposed promising vaccine antigen candidate in the "green" synthetic host Nicotiana benthamiana. Protein oligomerization strategies were implemented to increase the immunogenicity of the target antigen. Herein, the protein was expressed in oligomeric forms based on the C-terminally fused GCN4pII trimerization motif and GCN4pII_TP oligomerization motif. Quantitative western blot analysis showed significantly higher expression of trimeric CD2v ED_GCN4pII with a yield of about 12 mg/100 g of fresh weight, in comparison to oligomeric CD2v ED_GCN4pII_TP, revealing the former is the better choice for further studies. The results of purification and size determination by size exclusion chromatography (SEC) illustrated that CD2v ED_GCN4pII was successfully produced in stable oligomeric forms throughout the extraction, purification, and analysis process. Most importantly, purified CD2v ED_GCN4pII was demonstrated to induce both humoral and cellular immunity responses in mice to extents equivalent to those of the live attenuated vaccine ASFV-G-∆I177L, suggesting it as the potential subunit vaccine candidate for preventing ASFV.

基于植物的低聚物 CD2v 细胞外结构域抗原与减毒活疫苗 ASFV-G-∆I177L 具有相同的免疫原性。
由非洲猪瘟病毒(ASFV)引起的非洲猪瘟(ASF)是一种致命的高传染性疾病,家猪和野猪均可感染。该病死亡率高达 100%,对全球养猪业造成了严重影响。由于尚未发现有效的抗病毒治疗方法,疫苗接种等积极预防仍是控制疫情的关键。为了加快疫苗的开发,我们目前的工作首次报道了病毒外包膜糖蛋白 CD2v 细胞外结构域(CD2v ED)的异源生产,CD2v ED 是一种很有前景的候选疫苗抗原。为了提高目标抗原的免疫原性,我们采用了蛋白质寡聚化策略。在此,根据 C 端融合的 GCN4pII 三聚体化基调和 GCN4pII_TP 寡聚体化基调,以寡聚体形式表达了该蛋白。定量 Western 印迹分析表明,与低聚物 CD2v ED_GCN4pII_TP 相比,三聚体 CD2v ED_GCN4pII 的表达量明显更高,产量约为 12 mg/100 g 鲜重。通过尺寸排阻色谱法(SEC)进行纯化和尺寸测定的结果表明,在整个提取、纯化和分析过程中,CD2v ED_GCN4pII都以稳定的低聚物形式成功生产出来。最重要的是,纯化的 CD2v ED_GCN4pII 可诱导小鼠产生体液免疫和细胞免疫反应,其程度与 ASFV-G-∆I177L 减毒活疫苗相当,这表明它是预防 ASFV 的潜在亚单位候选疫苗。
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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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