Background

The four antigenically distinct serotypes of dengue virus (DENV) share extensive homology with each other and with the closely related Zika flavivirus (ZIKV). The development of polyclonal memory B cells (MBCs) to the four DENV serotypes and ZIKV during DENV infection is not fully understood.

Methods

Here we analyzed polyclonal MBCs at the single-cell level from peripheral blood mononuclear cells collected ~2 weeks or 6-7 months post-primary or post-secondary DENV infection from a pediatric hospital-based study in Nicaragua using a Multi-Color FluoroSpot assay.

Results

DENV elicits robust type-specific and cross-reactive MBC responses after primary and secondary DENV infection, with a significantly higher cross-reactive response in both. Reactivity to the infecting serotype dominated the total MBC response. While the frequency and proportion of type-specific and cross-reactive MBCs were comparable between primary and secondary DENV infections, within the cross-reactive response, the breadth of MBC responses against different serotypes was greater after secondary DENV infection. DENV infection also induced cross-reactive MBC responses recognizing ZIKV, particularly after secondary DENV infection.

Conclusions

Overall, our study sheds light on the polyclonal MBC response to DENV and ZIKV in naïve and DENV-pre-immune subjects, with important implications for natural infections and vaccine development.

中文翻译：

---

原发性和继发性登革热病毒感染会引起类似的记忆 B 细胞反应，但继发性登革热中对其他血清型的广度和对寨卡病毒的交叉反应性更高。

 背景

登革热病毒 (DENV) 的四种抗原性不同的血清型彼此之间以及与密切相关的寨卡黄病毒 (ZIKV) 具有广泛的同源性。 DENV 感染期间多克隆记忆 B 细胞 (MBC) 向四种 DENV 血清型和 ZIKV 的发育尚不完全清楚。

 方法

在此，我们使用多色 FluoroSpot 检测分析了单细胞水平的多克隆 MBC，这些单细胞来自于尼加拉瓜儿科医院研究中初发或继发 DENV 感染后约 2 周或 6-7 个月收集的外周血单核细胞。

 结果

在原发性和继发性 DENV 感染后，DENV 会引发强烈的类型特异性和交叉反应性 MBC 反应，并且两者的交叉反应性反应均显着较高。对感染血清型的反应主导了总 MBC 反应。虽然原发性和继发性 DENV 感染之间类型特异性和交叉反应性 MBC 的频率和比例相当，但在交叉反应反应中，继发性 DENV 感染后针对不同血清型的 MBC 反应的广度更大。 DENV 感染还诱导识别 ZIKV 的交叉反应性 MBC 反应，特别是在继发性 DENV 感染后。

 结论

总体而言，我们的研究揭示了未接触过 DENV 和 DENV 免疫前受试者对 DENV 和 ZIKV 的多克隆 MBC 反应，对自然感染和疫苗开发具有重要意义。