Department of Veterinary Medicine, College of Animal Science, Guizhou University, Guiyang, China.
Front Cell Infect Microbiol. 2024 Feb 29;13:1309096. doi: 10.3389/fcimb.2023.1309096. eCollection 2023.
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.
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.
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.
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.
山羊痘是由山羊痘病毒（GTPV）引起的一种严重传染病，给畜牧业造成了巨大的经济损失。传统的活减毒疫苗会引起严重的副作用，存在扩散的风险。因此，迫切需要开发高效、更安全的疫苗来预防和控制 GTPV。
本研究旨在采用免疫信息学方法设计一种针对 GTPV 的多表位亚单位疫苗。从 P32、L1R 和 095 蛋白筛选出 GTPV 的各种免疫优势细胞毒性 T 淋巴细胞（CTL）表位、辅助性 T 淋巴细胞（HTL）表位和 B 细胞表位，分别用 AAY、GPGPG 和 KK 接头连接。此外，用 EAAAK 接头将一个佐剂β-防御素连接到疫苗的 N 端，以增强其免疫原性。
构建的疫苗具有可溶性、无变应原性和非毒性，表现出高抗原性和免疫原性。随后对疫苗的 3D 结构进行预测、精修和验证，得到了一个优化模型，Z 值为-3.4。分子对接结果表明，疫苗与 TLR2（-27.25 kcal/mol）、TLR3（-39.84 kcal/mol）和 TLR4（-59.42 kcal/mol）具有较强的结合亲和力。分子动力学模拟结果表明，对接后的疫苗-TLR 复合物稳定。免疫模拟分析表明，该疫苗能显著提高 IgG 和 IgM 的抗体滴度，增加 IFN-γ 和 IL-2 的水平。
设计的 GTPV 多表位疫苗结构稳定，能诱导强烈的体液和细胞免疫应答，可能是一种有前途的 GTPV 疫苗候选物。
