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

机译:猪猪白细胞抗原(SLA)单倍型与B-和T细胞免疫应答对患者疾病病毒(FMDV)肽

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摘要

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.
机译:树枝状蛋白肽是对患有脚口病病毒(FMDV)的疫苗候选者。几种B细胞表位(B2T)树枝状大分子,携带VP1蛋白的主要FMDV抗原性B细胞位点,与来自3A和/或3D蛋白的异质T细胞表位共价连接,并引发一致的中和抗体和IFN-猪的产生细胞。为了解决猪MHC(SLA,猪白细胞抗原)对B2T树枝状大分子的免疫原性的高多态性质的贡献,进行低分辨率(LR)单倍型。我们研究了特定LR单倍型与B2T肽诱导的中和抗体和T细胞反应之间的可能相关性。在该研究中,分析了用B2T树枝状大分子和10种非免疫(对照)动物免疫的63只猪。结果揭示了SLA类-IL LR单倍型和T细胞响应之间的稳健性显着相关性。当样品还原到具有LR单倍型的动物时,才发现与SLA类-I LR单倍型和B细胞抗体反应和SLA类-I和SLA类II LR单倍型类似相关性的相关性。超过一次。这些结果支持SLA类-II限制T细胞对T细胞响应的幅度以及B2T树枝状大分子引起的抗体应答的贡献,对FMDV进行肽疫苗设计的潜在值。

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