Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides.

Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides.
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DOI:
10.3390/vaccines8030513
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发表时间:
2020-09-08
期刊:
影响因子:
7.8
通讯作者:
Hammer SE
Hammer SE
中科院分区:
医学3区
文献类型:
--
作者:
de León P;Cañas-Arranz R;Saez Y;Forner M;Defaus S;Cuadra D;Bustos MJ;Torres E;Andreu D;Blanco E;Sobrino F;Hammer SE

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树枝状肽是对抗口蹄疫病毒 (FMDV) 的有前途的候选疫苗。 VP1 蛋白中含有主要 FMDV 抗原 B 细胞位点的几种 B 细胞表位 (B2T) 树枝状聚合物与 3A 和/或 3D 蛋白的异型 T 细胞表位共价连接,并在猪体内引发一致水平的中和抗体和 IFN-γ 产生细胞。为了确定猪 MHC(SLA,猪白细胞抗原)的高度多态性对 B2T 树枝状聚合物免疫原性的影响,进行了低分辨率 (Lr) 单倍型分析。我们寻找具有中和抗体的特定 Lr 单倍型与 B2T 肽诱导的 T 细胞反应之间可能的相关性。在本研究中,分析了 63 头用 B2T 树状聚合物免疫的猪和 10 只未免疫(对照)的动物。结果揭示了 SLA II 类 Lr 单倍型与 T 细胞反应之间存在强大的显着相关性。 T 细胞反应与 SLA I 类 Lr 单倍型之间以及 B 细胞抗体反应与 SLA I 类和 SLA II 类 Lr 单倍型之间的相似相关性仅在样本减少到具有多次 Lr 单倍型的动物时才被发现。这些结果支持 SLA II 类限制性 T 细胞对 T 细胞反应强度和 B2T 树枝状聚合物引发的抗体反应的贡献,对于针对 FMDV 的肽疫苗设计具有潜在价值。
Dendrimer peptides are promising vaccine candidates against the foot-and-mouth disease virus (FMDV). Several B-cell epitope (B2T) dendrimers, harboring a major FMDV antigenic B-cell site in VP1 protein, are covalently linked to heterotypic T-cell epitopes from 3A and/or 3D proteins, and elicited consistent levels of neutralizing antibodies and IFN-γ-producing cells in pigs. To address the contribution of the highly polymorphic nature of the porcine MHC (SLA, swine leukocyte antigen) on the immunogenicity of B2T dendrimers, low-resolution (Lr) haplotyping was performed. We looked for possible correlations between particular Lr haplotypes with neutralizing antibody and T-cell responses induced by B2T peptides. In this study, 63 pigs immunized with B2T dendrimers and 10 non-immunized (control) animals are analyzed. The results reveal a robust significant correlation between SLA class-II Lr haplotypes and the T-cell response. Similar correlations of T-cell response with SLA class-I Lr haplotypes, and between B-cell antibody response and SLA class-I and SLA class-II Lr haplotypes, were only found when the sample was reduced to animals with Lr haplotypes represented more than once. These results support the contribution of SLA class-II restricted T-cells to the magnitude of the T-cell response and to the antibody response evoked by the B2T dendrimers, being of potential value for peptide vaccine design against FMDV.
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