Evaluating the Breadth of Neutralizing Antibody Responses Elicited by Infectious Bursal Disease Virus Genogroup A1 Strains Using a Novel Chicken B-Cell Rescue System and Neutralization Assay.

Evaluating the Breadth of Neutralizing Antibody Responses Elicited by Infectious Bursal Disease Virus Genogroup A1 Strains Using a Novel Chicken B-Cell Rescue System and Neutralization Assay.
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DOI:
10.1128/jvi.01255-22
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发表时间:
2022-09-28
影响因子:
5.4
通讯作者:
--
中科院分区:
医学2区
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根据传染性法氏囊病病毒(IBDV)衣壳高变区(HVR)的序列(A1-8),已经鉴定了8个基因组。鉴于报告的疫苗失败,有必要评估疫苗中和不同基因组的能力。为了解决这个问题,我们使用反向遗传学系统和鸡B细胞系DT 40来拯救一组嵌合IBDV并进行中和测定。嵌合病毒具有实验室适应株(PBG 98)的骨架和来自不同田间株的HVR:经典F52-70(A1)、US-变体Del-E(A2)、中国-变体SHG 19(A2)、极毒力UK 661(A3)、M04/09独特(A4)、意大利ITA-04(A6)和澳大利亚-变体维克-01/94(A8)。拯救的病毒在氨基酸位置253、284或330处没有显示出取代,这些取代之前被发现与细胞培养适应相关。来自接种wt(F52-70)或疫苗(228 E)A1毒株的鸡的血清具有针对Al病毒的最高平均病毒中和(VN)滴度(log 2 15.4和12.7),对A2病毒最低0001 - 0.0274),这与A1病毒在抗原性上最远离A2毒株一致,这与预测的HVR结构的差异程度相关。针对其他基因组的VN滴度范围为log 2 9.3-13.3,并且A1菌株与基因组A3和A4的抗原相关性可能比A6和A8更密切。我们的数据与现场观察结果一致,并验证了新方法,该方法可用于筛选未来的中和抗体候选疫苗,并评估不同基因组的抗原相关性。
Eight infectious bursal disease virus (IBDV) genogroups have been identified based on the sequence of the capsid hypervariable region (HVR) (A1-8). Given reported vaccine failures, there is a need to evaluate the ability of vaccines to neutralize the different genogroups. To address this, we used a reverse genetics system and the chicken B-cell line DT4O to rescue a panel of chimeric IBDVs and perform neutralization assays. Chimeric viruses had the backbone of a lab-adapted strain (PBG98) and the HVRs from diverse field strains: classical F52-70 (A1), US-variant Del-E (A2), Chinese-variant SHG19 (A2), very-virulent UK66l (A3), M04/09 distinct (A4), Italian ITA-04 (A6), and Australian-variant Vic-01/94 (A8). Rescued viruses showed no substitutions at amino-acid positions 253, 284, or 330, previously found to be associated with cell-culture adaptation. Sera from chickens inoculated with wt (F52-70) or vaccine (228E) A1 strains had the highest mean virus neutralization (VN) titers against the Al virus (log2 15.4 and 12.7), and the lowest against A2 viruses (log2 7.4-7.9, p=0.0001- 0.0274), consistent with Al viruses being most antigenically distant from A2 strains, which correlated with the extent of differences in the predicted HVR structure. VN titers against the other genogroups ranged from log2 9.3-13.3, and A1 strains were likely more closely antigenically related to genogroups A3 and A4 than A6 and A8. Our data are consistent with field observations and validate the new method which can used to screen future vaccine candidates for breadth of neutralizing antibodies, and evaluate the antigenic relatedness of different genogroups.
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