Dengue virus serotypes 1 to 4 (DENV1–4) and Zika virus (ZIKV) are mosquito-borne flaviviruses that induce both virus-specific and broadly reactive antibodies. A first DENV infection is thought to induce antibodies that wane over 2 years to titers that can subsequently enhance severe dengue disease. Secondary DENV infection with a different serotype is thought to induce stable, cross-serotype protective antibodies. Low dengue disease incidence after the recent Zika pandemic led to the hypothesis that ZIKV infection is also transiently cross protective. We investigated antibody kinetics in 4189 children up to 11 years after one and multiple DENV and ZIKV infections in longitudinal cohorts in Nicaragua. We used a DENV inhibition enzyme-linked immunosorbent assay (iELISA), which measures antibodies associated with protection against dengue and Zika disease and with enhancement of dengue disease severity. Unexpectedly, we found that overall DENV iELISA titers stabilized by 8 months after primary DENV infection to a half-life longer than a human life and waned, although gradually, after secondary DENV infection. Similarly, DENV iELISA titers were stable or rose after primary ZIKV infection but declined in individuals with histories of DENV and ZIKV infection. In contrast, kinetics of anti-ZIKV antibodies after ZIKV infection were similar regardless of prior DENV immunity. We observed heterogeneity in DENV iELISA titer, suggesting that individual antibody titer set point, rather than waning, is important for future dengue disease risk. Together, these findings change our understanding of anti-flavivirus antibody kinetics and have implications for measuring vaccine efficacy and for predicting future dengue and Zika outbreaks.

中文翻译：

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儿童中的登革热和寨卡病毒感染会引发长期存在的交叉反应性保护和增强抗体

登革热病毒血清型 1 至 4 (DENV1-4) 和寨卡病毒 (ZIKV) 是蚊媒黄病毒，可诱导病毒特异性和广泛反应性抗体。第一次 DENV 感染被认为会诱导抗体在 2 年内减弱至滴度，随后可加重严重的登革热病。具有不同血清型的继发性 DENV 感染被认为会诱导稳定的、跨血清型的保护性抗体。最近寨卡病毒大流行后的低登革热发病率导致假设寨卡病毒感染也具有短暂的交叉保护作用。我们在尼加拉瓜的纵向队列中研究了 4189 名儿童在一次和多次 DENV 和 ZIKV 感染后长达 11 年的抗体动力学。我们使用了 DENV 抑制酶联免疫吸附试验 (iELISA)，它测量与预防登革热和寨卡病以及增强登革热严重程度相关的抗体。出乎意料的是，我们发现总体 DENV iELISA 滴度在原发性 DENV 感染后 8 个月稳定到比人类寿命更长的半衰期，并且在继发性 DENV 感染后逐渐减弱。同样，DENV iELISA 滴度在原发性 ZIKV 感染后稳定或上升，但在有 DENV 和 ZIKV 感染史的个体中下降。相比之下，无论先前的 DENV 免疫如何，ZIKV 感染后抗 ZIKV 抗体的动力学都是相似的。我们观察到 DENV iELISA 滴度的异质性，表明个体抗体滴度设定点，而不是减弱，对未来的登革热疾病风险很重要。一起，