Multi-epitope vaccine

多表位疫苗
  • 文章类型: Journal Article
    布鲁氏菌病,由布鲁氏菌引起的人畜共患疾病,对动物和人类健康都构成重大威胁。在动物中,这种疾病会导致不孕,流产,高烧,而在人类中,症状可能包括反复发烧,疲劳,出汗,肝脾肿大,以及感染后的关节和肌肉疼痛。治疗通常包括长期抗生素治疗,给患者带来巨大的心理和经济负担。虽然接种疫苗对预防至关重要,目前的动物疫苗存在残留毒力等缺点,缺乏安全有效的人类疫苗。因此,布鲁氏菌病疫苗的开发势在必行。在这项研究中,我们利用生物信息学方法设计了一种针对布鲁氏菌的多表位疫苗。靶向血红素转运蛋白BhuA和多糖出口蛋白,我们鉴定了抗原表位,包括六个细胞毒性T淋巴细胞(CTL)优势表位,六个辅助性T淋巴细胞(HTL)优势表位,一个构象B细胞优势表位,和三个线性B细胞优势表位。通过将这些表位与适当的接头连接并掺入Toll样受体(TLR)激动剂(人β-防御素-2)和辅助肽(泛HLA-DR表位),我们构建了多表位疫苗(MEV)。MEV表现出高抗原性,无毒性,非过敏性,非人同源性,稳定性,和溶解度。分子对接分析和分子动力学模拟证实了MEV与受体的相互作用和稳定性(MHCI,MHCII,TLR4)。密码子优化和计算机克隆验证了MEV在大肠杆菌中的翻译效率和成功表达。免疫模拟进一步证明了MEV在诱导稳健免疫应答中的功效。总之,我们的研究结果表明,工程MEV有可能刺激体液和细胞免疫反应,为未来开发安全高效的布鲁氏菌疫苗提供有价值的见解。
    Brucellosis, a zoonotic disease caused by Brucella, presents a significant threat to both animal and human health. In animals, the disease can lead to infertility, miscarriage, and high fever, while in humans, symptoms may include recurrent fever, fatigue, sweating, hepatosplenomegaly, and joint and muscle pain following infection. Treatment often involves long-term antibiotic therapy, placing a substantial psychological and financial burden on patients. While vaccination is crucial for prevention, current animal vaccines have drawbacks such as residual virulence, and a safe and effective human vaccine is lacking. Hence, the development of a vaccine for brucellosis is imperative. In this study, we utilized bioinformatics methods to design a multi-epitope vaccine targeting Brucella. Targeting Heme transporter BhuA and polysaccharide export protein, we identified antigenic epitopes, including six cytotoxic T lymphocyte (CTL) dominant epitopes, six helper T lymphocyte (HTL) dominant epitopes, one conformation B cell dominant epitope, and three linear B cell dominant epitopes. By linking these epitopes with appropriate linkers and incorporating a Toll-like receptor (TLR) agonist (human beta-defensin-2) and an auxiliary peptide (Pan HLA-DR epitopes), we constructed the multi-epitope vaccine (MEV). The MEV demonstrated high antigenicity, non-toxicity, non-allergenicity, non-human homology, stability, and solubility. Molecular docking analysis and molecular dynamics simulations confirmed the interaction and stability of the MEV with receptors (MHCI, MHCII, TLR4). Codon optimization and in silico cloning validated the translation efficiency and successful expression of MEV in Escherichia coli. Immunological simulations further demonstrated the efficacy of MEV in inducing robust immune responses. In conclusion, our findings suggest that the engineered MEVs have the potential to stimulate both humoral and cellular immune responses, offering valuable insights for the future development of safe and efficient Brucella vaccines.
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  • 文章类型: Journal Article
    铜绿假单胞菌是一种复杂的医院感染因子,可导致多种疾病,其不断增长的抗性变化使治疗发展复杂化。研究强调了毒力因子OprE和OprF在发病机制中的重要性。强调他们作为候选疫苗的潜力。在这项研究中,B细胞,MHC-I,并鉴定了MHC-II表位,和分子接头有活性将这些表位与合适的佐剂连接以构建疫苗。采用了计算工具来预测三级框架,特点,并确认疫苗的成分。通过群体覆盖率分析和免疫模拟对效力进行称重。该项目旨在利用免疫信息学资源创建一种多表位疫苗,以减少铜绿假单胞菌相关疾病和死亡率。最终的复合物被确定为稳定的,可溶性,抗原性,并且在检查其物理化学和免疫学特性时不过敏。此外,蛋白质表现出酸性和亲水性特征。Ramachandran的阴谋,ProSA-Web,ERRAT,一旦蛋白质的三维结构被建立和完善,Verify3D被用来确保最终模型的真实性。当与MHC受体相互作用时,疫苗模型显示出显著的结合评分和稳定性。人口覆盖率分析表明,全球覆盖率为83.40%,美国的覆盖率最高,超过90%。此外,在将疫苗序列克隆到EcoRI和EcoRV限制性位点的大肠杆菌质粒载体pET-28a(+)之前,对疫苗序列进行了密码子优化.我们的研究开发了一种针对铜绿假单胞菌的疫苗,该疫苗具有很强的结合亲和力和全球覆盖率,提供一种可接受的方法来减轻医院感染。
    Pseudomonas aeruginosa is a complex nosocomial infectious agent responsible for numerous illnesses, with its growing resistance variations complicating treatment development. Studies have emphasized the importance of virulence factors OprE and OprF in pathogenesis, highlighting their potential as vaccine candidates. In this study, B-cell, MHC-I, and MHC-II epitopes were identified, and molecular linkers were active to join these epitopes with an appropriate adjuvant to construct a vaccine. Computational tools were employed to forecast the tertiary framework, characteristics, and also to confirm the vaccine\'s composition. The potency was weighed through population coverage analysis and immune simulation. This project aims to create a multi-epitope vaccine to reduce P. aeruginosa-related illness and mortality using immunoinformatics resources. The ultimate complex has been determined to be stable, soluble, antigenic, and non-allergenic upon inspection of its physicochemical and immunological properties. Additionally, the protein exhibited acidic and hydrophilic characteristics. The Ramachandran plot, ProSA-web, ERRAT, and Verify3D were employed to ensure the final model\'s authenticity once the protein\'s three-dimensional structure had been established and refined. The vaccine model showed a significant binding score and stability when interacting with MHC receptors. Population coverage analysis indicated a global coverage rate of 83.40%, with the USA having the highest coverage rate, exceeding 90%. Moreover, the vaccine sequence underwent codon optimization before being cloned into the Escherichia coli plasmid vector pET-28a (+) at the EcoRI and EcoRV restriction sites. Our research has developed a vaccine against P. aeruginosa that has strong binding affinity and worldwide coverage, offering an acceptable way to mitigate nosocomial infections.
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  • 文章类型: Journal Article
    新生隐球菌是一种分布广泛的机会性病原真菌。虽然新生隐球菌通常感染免疫功能低下的个体,它也会影响那些有免疫能力的人。新生隐球菌的传播主要通过呼吸道发生,导致脑膜炎的发展。隐球菌性脑膜炎的死亡率很高,和治疗选择是有限的。新生隐球菌感染构成了重大的公共卫生威胁,目前缺乏有针对性和有效的应对策略。本研究旨在筛选T淋巴细胞(CTL,来自四种新生隐球菌抗原的HTL)和B淋巴细胞(LBL)表位,并通过将它们与各种佐剂组合来开发两种多表位疫苗。分子对接结果表明,该疫苗与TLR4稳定结合并诱导先天免疫。通过后续分子动力学模拟验证了分子对接结果的可信度。此外,免疫模拟分析的结果强调了多表位疫苗在宿主生物体内有效诱导强大的体液和细胞免疫应答的能力。这两种疫苗已经证明了对新生隐球菌感染的理论功效,如计算机分析所示。然而,额外的实验验证对于证实疫苗的保护效力至关重要.
    使用生物信息学方法设计了涵盖最常见的A和D表型的多表位新生隐球菌疫苗。
    Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While Cryptococcus neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of Cryptococcus neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte(CTL, HTL) and B lymphocyte (LBL) epitopes derived from four Cryptococcus neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to TLR4 and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine\'s capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against Cryptococcus neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.
    A multi-epitope Cryptococcus neoformans vaccine covering the most common A and D phenotypes was designed using bioinformatics methods.
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  • 文章类型: Journal Article
    当前的结核病(TB)控制策略面临局限性,如抗生素治疗依从性低和多药耐药性上升。此外,缺乏安全有效的疫苗化合物这些挑战。现有疫苗对结核病的疗效有限,这凸显了创新战略的紧迫性。如免疫信息学。因此,本研究旨在利用免疫信息学方法设计针对结核感染的靶向多表位疫苗.
    针对Ag85A的多表位疫苗,Ag85B,ESAT-6和CFP-10蛋白。该设计采用了细胞毒性T淋巴细胞(CTL)的各种免疫信息学工具,辅助性T淋巴细胞(HTL),和线性B淋巴细胞(LBL)表位预测,对疫苗特性的评估,结构建模,人口覆盖率分析,二硫化物工程,溶解度预测,与Toll样受体(TLRs)的分子对接/动力学,密码子优化/克隆,和免疫模拟。
    多表位疫苗,它是用12个CTL组装的,25HTL,和21个与CpG佐剂相关的LBL表位,表现出了有希望的特点。免疫信息学分析证实了抗原性,免疫原性,缺乏过敏原性。物理化学评估表明蛋白质是稳定的,热稳定,亲水性,并且高度可溶。对接模拟表明与TLR的高亲和力结合,包括TLR2、TLR4和TLR9。计算机免疫模拟预测了强T细胞(细胞因子释放)和B细胞(免疫球蛋白释放)反应。
    这种免疫信息学设计的多表位疫苗靶向Ag85A,Ag85B,ESAT-6和CFP-10蛋白在稳定性方面显示出有希望的特征,免疫原性,抗原性,溶解度,并预测体液和适应性免疫反应的诱导。这表明其作为针对TB的预防性和治疗性疫苗的潜力。
    UNASSIGNED: Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores the urgency for innovative strategies, such as immunoinformatics. Consequently, this study aimed to design a targeted multi-epitope vaccine against TB infection utilizing an immunoinformatics approach.
    UNASSIGNED: The multi-epitope vaccine targeted Ag85A, Ag85B, ESAT-6, and CFP-10 proteins. The design adopted various immunoinformatics tools for cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitope prediction, the assessment of vaccine characteristics, structure modeling, population coverage analysis, disulfide engineering, solubility prediction, molecular docking/dynamics with toll-like receptors (TLRs), codon optimization/cloning, and immune simulation.
    UNASSIGNED: The multi-epitope vaccine, which was assembled using 12 CTL, 25 HTL, and 21 LBL epitopes associated with CpG adjuvants, showed promising characteristics. The immunoinformatics analysis confirmed the antigenicity, immunogenicity, and lack of allergenicity. Physicochemical evaluations indicated that the proteins were stable, thermostable, hydrophilic, and highly soluble. Docking simulations suggested high-affinity binding to TLRs, including TLR2, TLR4, and TLR9. In silico immune simulation predicted strong T cell (cytokine release) and B cell (immunoglobulin release) responses.
    UNASSIGNED: This immunoinformatics-designed multi-epitope vaccine targeting Ag85A, Ag85B, ESAT-6, and CFP-10 proteins showed promising characteristics in terms of stability, immunogenicity, antigenicity, solubility, and predicted induction of humoral and adaptive immune responses. This suggests its potential as a prophylactic and therapeutic vaccine against TB.
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  • 文章类型: Journal Article
    目的:叶酸受体α(FRα)在>90%的高级别上皮性卵巢癌(EOC)中过表达。用抗体-药物缀合物靶向FRα已被证明在铂抗性环境中具有实用性。它也是免疫肿瘤药物的潜在治疗靶点,例如主要通过适应性和体液免疫起作用的肽疫苗。我们测试了以下假设:FRα肽免疫可以改善EOC患者对基于铂的治疗产生反应后的预后。
    方法:我们进行了随机,双盲,多中心,II期研究旨在评估TPIV200(一种与GM-CSF混合的多表位FRα肽疫苗)与单独GM-CSF的安全性和有效性,这些女性在至少4个周期的一线铂类治疗后没有疾病进展。患者每4周一次皮内接种疫苗,最多6次,随后是12周间隔的6次疫苗接种的加强期。主要终点包括安全性,耐受性,无进展生存期(PFS)。
    结果:在研究终止时,中位随访时间为15.2个月(范围1.2-28.4个月),119例意向治疗患者中有68例出现疾病进展(TPIV200+GM-CSF组55%,单独GM-CSF组59%)。中位PFS为11.1个月(95%CI8.3-16.6个月),治疗组之间无显着差异(TPIV200GM-CSF为10.9个月,GM-CSF为11.1个月,HR,0.85;上限90%CI1.17]。无患者经历≥3级药物相关不良事件。
    结论:TPIV200耐受性良好,但与PFS改善无关。需要额外的研究来揭示使用靶向FRa的多表位疫苗的潜在协同作用。试用注册NLM/NCBI注册中心,NCT02978222,https://clinicaltrials.gov/search?term=NCT02978222.
    OBJECTIVE: Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity. We tested the hypothesis that FRα peptide immunization could improve outcomes in patients with EOC following response to platinum-based therapy.
    METHODS: We conducted a randomized, double-blind, multicenter, phase II study to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF) versus GM-CSF alone in 120 women who did not have disease progression after at least 4 cycles of first-line platinum-based therapy. Patients were vaccinated intradermally once every 4 weeks up to 6 times, followed by a boosting period of 6 vaccinations at 12-week intervals. Primary endpoints included safety, tolerability, and progression free survival (PFS).
    RESULTS: At study termination with a median follow-up of 15.2 months (range 1.2-28.4 months), 68 of 119 intention-to-treat patients had disease progression (55% in TPIV200 + GM-CSF arm and 59% in GM-CSF alone arm). The median PFS was 11.1 months (95% CI 8.3-16.6 months) with no significant difference between the treatment groups (10.9 months with TPIV200 + GM-CSF versus 11.1 months with GM-CSF, HR, 0.85; upper 90% CI 1.17]. No patient experienced a ≥ grade 3 drug-related adverse event.
    CONCLUSIONS: TPIV200 was well tolerated but was not associated with improved PFS. Additional studies are required to uncover potential synergies using multiepitope vaccines targeting FRα. Trial Registration NLM/NCBI Registry, NCT02978222, https://clinicaltrials.gov/search?term=NCT02978222.
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  • 文章类型: Journal Article
    猪轮状病毒(PoRV)是影响全球猪饲养地区的重要病原体,对畜牧业的经济发展构成重大威胁。目前,没有针对这种疾病的特定药物,和治疗选择仍然非常有限。这项研究旨在设计一种用于PoRV的多表位肽疫苗,采用生物信息学方法来稳健地激活T细胞和B细胞免疫应答。两种抗原蛋白,VP7和VP8*,选自PoRV,使用免疫信息学工具预测潜在的免疫原性T细胞和B细胞表位。根据无毒性进一步筛选这些表位,抗原性,非过敏性,和免疫原性标准。选择的表位与接头连接以形成新的多表位疫苗构建体。PADRE序列(AKFVAAAWTLKAAA)和RS09肽连接在设计的肽链的N末端,以增强疫苗的抗原性。使用计算方法进行疫苗构建体与toll样受体(TLR3和TLR4)的蛋白质-蛋白质对接,选择能量最低的对接结果作为最优预测模型。随后,分子动力学(MD)模拟方法用于评估蛋白质疫苗构建体以及TLR3和TLR4受体的稳定性。结果表明,疫苗-TLR3和疫苗-TLR4对接模型在整个模拟期间保持稳定。此外,C-IMMSIM工具用于确定疫苗蛋白的免疫原性触发能力,证明构建的疫苗蛋白可以诱导细胞介导和体液免疫反应,从而在引发宿主免疫反应中发挥作用。总之,本研究成功构建了针对PoRV的多表位疫苗,并通过计算分析验证了疫苗的稳定性和有效性。然而,由于这项研究是纯粹计算的,需要进行实验评估以验证新构建的疫苗蛋白的安全性和免疫原性。
    Porcine Rotavirus (PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine\'s antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.
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  • 文章类型: Journal Article
    目的:引起肠道疾病的病原微生物可显著危害人类健康。目前,没有授权的治疗或疫苗接种来对抗导致肠道疾病的细菌。
    方法:使用免疫信息学,我们开发了一种有效的多表位组合(组合)疫苗对抗沙门氏菌和肠出血性大肠杆菌。B和T细胞表位通过进行保护性评估来鉴定,人口覆盖率分析,物理化学属性评估,以及所选择的抗原多肽的二级和三级结构评估。疫苗开发的选择过程包括使用几种生物信息学工具和方法最终选择两个线性B细胞表位,5个CTL表位,和两个HTL表位。
    结果:该疫苗具有很强的免疫原性,细胞因子产生,免疫学特性,无毒性,非过敏性,稳定性,以及对感染的潜在功效。二硫化物粘结,密码子修饰,和计算克隆也用于增强在宿主大肠杆菌中表达的稳定性和功效。该疫苗的结构对TLR4配体具有很强的亲和力,并且非常耐用,如分子对接和分子建模所示。免疫学模拟的结果表明B细胞和T细胞都对疫苗接种组分具有增强的应答。
    结论:全面的计算机分析显示,所提出的疫苗可能会引发针对引起肠道疾病的病原菌的强大免疫反应。因此,对于进一步的实验测试,这是一个很有希望的选择。
    OBJECTIVE: The pathogenic microorganisms that cause intestinal diseases can significantly jeopardize people\'s health. Currently, there are no authorized treatments or vaccinations available to combat the germs responsible for intestinal disease.
    METHODS: Using immunoinformatics, we developed a potent multi-epitope Combination (combo) vaccine versus Salmonella and enterohemorrhagic E. coli. The B and T cell epitopes were identified by performing a conservancy assessment, population coverage analysis, physicochemical attributes assessment, and secondary and tertiary structure assessment of the chosen antigenic polypeptide. The selection process for vaccine development included using several bioinformatics tools and approaches to finally choose two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes.
    RESULTS: The vaccine had strong immunogenicity, cytokine production, immunological properties, non-toxicity, non-allergenicity, stability, and potential efficacy against infections. Disulfide bonding, codon modification, and computational cloning were also used to enhance the stability and efficacy of expression in the host E. coli. The vaccine\'s structure has a strong affinity for the TLR4 ligand and is very durable, as shown by molecular docking and molecular modeling. The results of the immunological simulation demonstrated that both B and T cells had a heightened response to the vaccination component.
    CONCLUSIONS: The comprehensive in silico analysis reveals that the proposed vaccine will likely elicit a robust immune response against pathogenic bacteria that cause intestinal diseases. Therefore, it is a promising option for further experimental testing.
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  • 文章类型: Journal Article
    结核病是由结核分枝杆菌(Mtb)引起的高度传染性疾病,这是全球数百万人死亡的主要原因之一。这种细菌的死亡率比其他细菌疾病高得多,耐药菌株的迅速上升只会使情况更加令人担忧。目前,唯一获得许可的疫苗BCG(BacillusCalmette-Guérin)在预防成人肺结核预防和潜伏性肺结核再激活方面无效.因此,迫切需要找到提供强大免疫防御并具有多种应用的新型安全疫苗。结合来自多种候选蛋白的表位的疫苗已显示出增强针对Mtb感染的免疫力。本研究采用免疫信息学策略,使用五种抗原蛋白对Mtb进行适当的多表位免疫。潜在的B细胞,细胞毒性T淋巴细胞,和辅助性T淋巴细胞表位从预期的蛋白质推测,并与50s核糖体L7/L12佐剂偶联,并且制造了疫苗。疫苗的物理化学特征证明了抗原性,可溶性,不过敏。同时,对接,分子动力学模拟,和必要动力学分析表明,多表位疫苗结构与Toll样受体(TLR2和TLR3)相互作用强烈。进行MM-PBSA分析以准确确定系统的分子间结合自由能。将免疫模拟应用于疫苗以预测其免疫原性。最后,计算机克隆用于验证疫苗的功效。免疫信息学分析提示多表位疫苗可诱导特异性免疫应答,使其成为对抗Mtb的潜在候选人。然而,通过对开发疫苗的体内研究进行验证对于评估其功效和免疫原性特征至关重要,这将确保对Mtb的积极保护。
    Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis (Mtb), which is one of the prominent reasons for the death of millions worldwide. The bacterium has a substantially higher mortality rate than other bacterial diseases, and the rapid rise of drug-resistant strains only makes the situation more concerning. Currently, the only licensed vaccine BCG (Bacillus Calmette-Guérin) is ineffective in preventing adult pulmonary tuberculosis prophylaxis and latent tuberculosis re-activation. Therefore, there is a pressing need to find novel and safe vaccines that provide robust immune defense and have various applications. Vaccines that combine epitopes from multiple candidate proteins have been shown to boost immunity against Mtb infection. This study applies an immunoinformatic strategy to generate an adequate multi-epitope immunization against Mtb employing five antigenic proteins. Potential B-cell, cytotoxic T lymphocyte, and helper T lymphocyte epitopes were speculated from the intended proteins and coupled with 50 s ribosomal L7/L12 adjuvant, and the vaccine was constructed. The vaccine\'s physicochemical profile demonstrates antigenic, soluble, and non-allergic. In the meantime, docking, molecular dynamics simulations, and essential dynamics analysis revealed that the multi-epitope vaccine structure interacted strongly with Toll-like receptors (TLR2 and TLR3). MM-PBSA analysis was performed to ascertain the system\'s intermolecular binding free energies accurately. The immune simulation was applied to the vaccine to forecast its immunogenic profile. Finally, in silico cloning was used to validate the vaccine\'s efficacy. The immunoinformatics analysis suggests the multi-epitope vaccine could induce specific immune responses, making it a potential candidate against Mtb. However, validation through the in-vivo study of the developed vaccine is essential to assess its efficacy and immunogenicity profile, which will assure active protection against Mtb.
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  • 文章类型: Journal Article
    马尔堡病毒(MARV)是一种高度传染性和毒性的病原体,属于丝状病毒科。MARV在人类和非人类灵长类动物中引起严重的出血热。由于其剧毒性质,预防性方法对其控制是有希望的。目前没有批准的针对MARV的药物或疫苗,管理主要包括支持性护理,以治疗症状和预防并发症。我们的目的是使用免疫信息学研究设计一种针对MARV的新型多表位疫苗(MEV)。在这项研究中,使用各种蛋白质(VP35、VP40和糖蛋白前体)并选择潜在的表位。CTL和HTL表位覆盖了79.44%和70.55%的全球人口,分别。设计的MEV构建体稳定并在大肠杆菌中表达(E.大肠杆菌)宿主。物理化学性质也是可接受的。MARVMEV候选物可以预测综合免疫反应,例如体液和细胞的免疫反应。此外,预测了与toll样受体3(TLR3)及其激动剂(β-防御素)的有效相互作用。需要使用进一步的体外和体内研究来验证这些结果。
    Marburg virus (MARV) is a highly contagious and virulent agent belonging to Filoviridae family. MARV causes severe hemorrhagic fever in humans and non-human primates. Owing to its highly virulent nature, preventive approaches are promising for its control. There is currently no approved drug or vaccine against MARV, and management mainly involves supportive care to treat symptoms and prevent complications. Our aim was to design a novel multi-epitope vaccine (MEV) against MARV using immunoinformatics studies. In this study, various proteins (VP35, VP40 and glycoprotein precursor) were used and potential epitopes were selected. CTL and HTL epitopes covered 79.44% and 70.55% of the global population, respectively. The designed MEV construct was stable and expressed in Escherichia coli (E. coli) host. The physicochemical properties were also acceptable. MARV MEV candidate could predict comprehensive immune responses such as those of humoral and cellular in silico. Additionally, efficient interaction to toll-like receptor 3 (TLR3) and its agonist (β-defensin) was predicted. There is a need for validation of these results using further in vitro and in vivo studies.
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  • 文章类型: Journal Article
    查加斯病,由原生动物克氏锥虫引起的,仍然是影响拉丁美洲和全世界数百万人的重大公共卫生挑战。尽管在病媒控制方面取得了重大进展,不存在预防感染或减轻疾病发病机制的疫苗。我们开发了一种合理设计的嵌合蛋白疫苗,N-Tc52/TSkb20,结合了两种克氏锥虫抗原的免疫显性表位,Tc52的氨基末端部分和来自转唾液酸酶的TSkb20表位。这项研究的目的是构建和表征抗原,并评估其在T.cruzi感染的免疫预防小鼠模型中的保护潜力。N-Tc52/TSkb20蛋白在大肠杆菌中重组表达,并使用质谱和蛋白质印迹确认其身份。用嵌合蛋白免疫显着控制寄生虫血症并减少心脏,结肠,和与未接种疫苗的小鼠相比的骨骼肌寄生虫负担。保护优于用个体亲本抗原组分接种。机械上,该疫苗诱导了针对掺入表位的有效CD8+T细胞和IFNγ应答以及保护性IgG抗体谱。相对较低的IL-10反应有利于早期寄生虫控制。这些结果验证了有希望的多表位方法,并支持了针对恰加斯病的此类合理疫苗设计策略的持续开发。
    Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health challenge affecting millions in Latin America and worldwide. Although significant progress has been made in vector control, no vaccine exists to prevent infection or mitigate disease pathogenesis. We developed a rationally designed chimeric protein vaccine, N-Tc52/TSkb20, incorporating immunodominant epitopes from two T. cruzi antigens, the amino-terminal portion of Tc52 and the TSkb20 epitope derived from trans-sialidase. The objectives of this study were to construct and characterize the antigen and evaluate its protective potential in an immunoprophylactic murine model of T. cruzi infection. The N-Tc52/TSkb20 protein was recombinantly expressed in E. coli and its identity was confirmed using mass spectrometry and Western blotting. Immunization with the chimeric protein significantly controlled parasitemia and reduced the heart, colon, and skeletal muscle parasite burdens compared to non-vaccinated mice. Protection was superior to vaccination with the individual parental antigen components. Mechanistically, the vaccine induced potent CD8+ T-cell and IFNγ responses against the incorporated epitopes and a protective IgG antibody profile. A relatively low IL-10 response favored early parasite control. These results validate the promising multi-epitope approach and support the continued development of this type of rational vaccine design strategy against Chagas disease.
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