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Hypervariable antigenic region 1 of classical swine fever virus E2 protein impacts antibody neutralization

机译:古典猪瘟病毒E2蛋白的高变抗原区域1抗体中和

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Envelope glycoprotein E2 of classical swine fever virus (CSFV) is the major antigen that induces neutralizing antibodies and confers protection against CSFV infection. There are three hypervariable antigenic regions (HAR1, HAR2 and HAR3) of E2 that are different between the group 1 vaccine C-strain and group 2 clinical isolates. This study was aimed to characterize the antigenic epitope region recognized by monoclonal antibody 4F4 (mAb-4F4) that is present in the group 2 field isolate HZ1-08, but not in the C-strain, and examine its impact on neutralization titers when antisera from different recombinant viruses were cross-examined. Indirect ELISA with C-strain E2-based chimeric proteins carrying the three HAR regions showed that the mAb-4F4 bound to HAR1 from HZ1-08 E2, but not to HAR2 or HAR3, indicating that the specific epitope is located in the HAR1 region. Of the 6 major residues differences between C-strain and field isolates, Glu713 in the HAR1 region of strain HZ1-08 is critical for mAb-4F4 binding either at the recombinant protein level or using intact recombinant viruses carrying single mutations. C-strain based recombinant viruses carrying the most antigenic part of E2 or HAR1 from strain HZ1-08 remained non-pathogenic to pigs and induced good antibody responses. By cross-neutralization assay, we observed that the anti-C-strain serum lost most of its neutralization capacity to RecC-HZ-E2 and QZ-14 (subgroup 2.1d field isolate in 2014), and vice versa. More importantly, the RecC-HAR1 virus remained competent in neutralizing ReC-HZ-E2 and QZ-14 strains without compromising the neutralization capability to the recombinant C-strain. Thus, we propose that chimeric C-strain carrying the HART region of field isolates is a good vaccine candidate for classical swine fever. (C) 2016 Elsevier Ltd. All rights reserved.
机译:典型猪瘟病毒(CSFV)的封套糖蛋白E2是诱导中和抗体的主要抗原,并赋予CSFV感染保护。在第1族疫苗C-菌株和第2组临床分离株之间存在三种高变抗原区域(HAR1,HAR2和HAR3)。该研究旨在表征由单克隆抗体4F4(MAB-4F4)识别的抗原表位区域,其存在于第2族分离物HZ1-08中但不在C-菌株中,并在抗血清时检查其对中和滴度的影响来自不同的重组病毒被交叉检查。携带三个HAR区域的基于C-菌株E2的嵌合蛋白的间接ELISA显示,MAB-4F4与HAX1-08 E2结合的MAB-4F4,但不是HAR2或HAR3,表明特定表位位于HAR1区域中。在菌株和场分离株之间的6个主要残留物中,菌株HZ1-08的HAR1区域中的GLU713对于在重组蛋白水平或使用携带单一突变的完整重组病毒的MAB-4F4结合至关重要。基于C-菌株的重组病毒从菌株HZ1-08携带e2或Har1的最抗原部分仍然是猪的非致病性,并且诱导良好的抗体反应。通过交叉中和测定,我们观察到抗C-菌株血清对RECC-HZ-E2和QZ-14的大部分中和能力失去了大部分中和能力(2014年亚组2.1D场隔离),反之亦然。更重要的是,RECC-HAR1病毒残留在中和REC-HZ-E2和QZ-14菌株的情况下,而不会影响重组C-菌株的中和能力。因此,我们提出携带野外分离株HART区域的嵌合C-菌株是典型猪瘟的良好疫苗候选者。 (c)2016 Elsevier有限公司保留所有权利。

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