OBJECTIVES Zika virus (ZIKV) is a mosquito-borne flavivirus that re-emerged in 2015. The association between ZIKV and neurological complications initiated the development of relevant animal models to understand the mechanisms underlying ZIKV-induced pathologies. Transient inhibition of the type I interferon (IFN) pathway through the use of an IFNAR1-blocking antibody, MAR1-5A3, could efficiently permit active virus replication in immunocompetent animals. Type I IFN signalling is involved in the regulation of humoral responses, and thus, it is crucial to investigate the potential effects of type I IFN blockade towards B-cell responses. METHODS In this study, comparative analysis was conducted using serum samples collected from ZIKV-infected wild-type (WT) animals either administered with or without MAR1-5A3. RESULTS Serological assays revealed a more robust ZIKV-specific IgG response and subtype switching upon inhibition of type I IFN due to the abundance of antigen availability. This observation was corroborated by an increase in germinal centres, plasma cells and germinal centre B cells. Interestingly, although both groups of animals recognised different B-cell linear epitopes in the E and NS1 regions, there was no difference in neutralising capacity. Further characterisation of these epitopes in the E protein revealed a detrimental role of antibodies that were generated in the absence of type I IFN. CONCLUSION This study highlights the role of type I IFN in shaping the anti-ZIKV antibody response to generate beneficial antibodies and will help guide development of better vaccine candidates triggering efficient neutralising antibodies and avoiding detrimental ones.

中文翻译：

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I 型干扰素决定了抗寨卡病毒抗体反应的数量和质量。

目标 寨卡病毒 (ZIKV) 是一种蚊媒黄病毒，于 2015 年重新出现。寨卡病毒与神经系统并发症之间的关联启动了相关动物模型的开发，以了解寨卡病毒诱导的病理机制。通过使用 IFNAR1 阻断抗体 MAR1-5A3 对 I 型干扰素 (IFN) 途径的瞬时抑制可以有效地允许免疫活性动物中的活跃病毒复制。I 型 IFN 信号传导参与体液反应的调节，因此，研究 I 型 IFN 阻断对 B 细胞反应的潜在影响至关重要。方法 在这项研究中，使用从感染 ZIKV 的野生型 (WT) 动物中收集的血清样本进行比较分析，无论是否使用 MAR1-5A3。结果 血清学分析显示，由于抗原可用性丰富，抑制 I 型 IFN 后，ZIKV 特异性 IgG 反应和亚型转换更加稳健。生发中心、浆细胞和生发中心 B 细胞的增加证实了这一观察结果。有趣的是，尽管两组动物在 E 区和 NS1 区都识别出不同的 B 细胞线性表位，但中和能力没有差异。对 E 蛋白中这些表位的进一步表征揭示了在没有 I 型干扰素的情况下产生的抗体的有害作用。