关键词: epitope vaccine goatpox virus immune simulation immunoinformatics molecular docking molecular dynamics

Mesh : Molecular Docking Simulation Immunoinformatics Capripoxvirus Epitopes, T-Lymphocyte Computational Biology / methods Epitopes, B-Lymphocyte Viral Vaccines Molecular Dynamics Simulation Vaccines, Subunit

来  源:   DOI:10.3389/fcimb.2023.1309096   PDF(Pubmed)

Abstract:
UNASSIGNED: Goatpox, a severe infectious disease caused by goatpox virus (GTPV), leads to enormous economic losses in the livestock industry. Traditional live attenuated vaccines cause serious side effects and exist a risk of dispersal. Therefore, it is urgent to develop efficient and safer vaccines to prevent and control of GTPV.
UNASSIGNED: In the present study, we are aimed to design a multi-epitope subunit vaccine against GTPV using an immunoinformatics approach. Various immunodominant cytotoxic T lymphocytes (CTL) epitopes, helper T lymphocytes (HTL) epitopes, and B-cell epitopes from P32, L1R, and 095 proteins of GTPV were screened and liked by the AAY, GPGPG, and KK connectors, respectively. Furthermore, an adjuvant β-defensin was attached to the vaccine\'s N-terminal using the EAAAK linker to enhance immunogenicity.
UNASSIGNED: The constructed vaccine was soluble, non-allergenic and non-toxic and exhibited high levels of antigenicity and immunogenicity. The vaccine\'s 3D structure was subsequently predicted, refined and validated, resulting in an optimized model with a Z-value of -3.4. Molecular docking results demonstrated that the vaccine had strong binding affinity with TLR2(-27.25 kcal/mol), TLR3(-39.84 kcal/mol), and TLR4(-59.42 kcal/mol). Molecular dynamics simulation results indicated that docked vaccine-TLR complexes were stable. Immune simulation analysis suggested that the vaccine can induce remarkable increase in antibody titers of IgG and IgM, higher levels of IFN-γ and IL-2.
UNASSIGNED: The designed GTPV multi-epitope vaccine is structurally stable and can induce robust humoral and cellular immune responses, which may be a promising vaccine candidate against GTPV.
摘要:
山痘,一种由山羊痘病毒(GTPV)引起的严重传染病,给畜牧业造成了巨大的经济损失。传统的减毒活疫苗会引起严重的副作用,并存在传播的风险。因此,迫切需要开发高效,更安全的疫苗来预防和控制GTPV。
在本研究中,我们的目的是使用免疫信息学方法设计针对GTPV的多表位亚单位疫苗.各种免疫显性细胞毒性T淋巴细胞(CTL)表位,辅助性T淋巴细胞(HTL)表位,和来自P32,L1R的B细胞表位,AY对GTPV的095个蛋白质进行了筛选和筛选,GPG,和KK连接器,分别。此外,使用EAAAK接头将佐剂β-防御素连接到疫苗的N末端以增强免疫原性。
构建的疫苗是可溶性的,非过敏性和无毒,并表现出高水平的抗原性和免疫原性。随后预测了疫苗的3D结构,精炼和验证,得到Z值为-3.4的优化模型。分子对接结果表明,该疫苗与TLR2(-27.25kcal/mol)有较强的结合亲和力,TLR3(-39.84kcal/mol),和TLR4(-59.42kcal/mol)。分子动力学模拟结果表明对接的疫苗-TLR复合物是稳定的。免疫模拟分析表明,该疫苗可诱导IgG和IgM抗体滴度显著升高,更高水平的IFN-γ和IL-2。
设计的GTPV多表位疫苗结构稳定,可以诱导强大的体液和细胞免疫反应,这可能是一个有前途的候选疫苗抗GTPV。
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