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Abstract：
Between 2016 and 2018, Brazil experienced major sylvatic yellow fever (YF) outbreaks that caused hundreds of casualties, with Minas Gerais (MG) being the most affected state. These outbreaks provided a unique opportunity to assess the immune response triggered by the wild-type (WT) yellow fever virus (YFV) in humans. The plaque reduction neutralization test (PRNT) is currently the standard method to assess the humoral immune response to YFV by measuring neutralizing antibodies (nAbs). The present study aimed to evaluate the humoral immune response of patients from the 2017-2018 sylvatic YF outbreak in MG with different disease outcomes by using PRNTs with a WT YFV strain, isolated from the 2017-2018 outbreak, and a vaccine YFV strain. Samples from naturally infected YF patients were tested, in comparison with healthy vaccinees. Results showed that both groups presented different levels of nAb against the WT and vaccine strains, and the levels of neutralization against the strains varied homotypically and heterotypically. Results based on the geometric mean titers (GMTs) suggest that the humoral immune response after a natural infection of YFV can reach higher levels than that induced by vaccination (GMT of patients against WT YFV compared to GMT of vaccinees, P < 0.0001). These findings suggest that the humoral immune responses triggered by the vaccine and WT strains of YFV are different, possibly due to genetic and antigenic differences between these viruses. Therefore, current means of assessing the immune response in naturally infected YF individuals and immunological surveillance methods in areas with intense viral circulation may need to be updated.IMPORTANCEYellow fever is a deadly febrile disease caused by the YFV. Despite the existence of effective vaccines, this disease still represents a public health concern worldwide. Much is known about the immune response against the vaccine strains of the YFV, but recent studies have shown that it differs from that induced by WT strains. The extent of this difference and the mechanisms behind it are still unclear. Thus, studies aimed to better understand the immune response against this virus are relevant and necessary. The present study evaluated levels of neutralizing antibodies of yellow fever patients from recent outbreaks in Brazil, in comparison with healthy vaccinees, using plaque reduction neutralization tests with WT and vaccine YFV strains. Results showed that the humoral immune response in naturally infected patients was higher than that induced by vaccination, thus providing new insights into the immune response triggered against these viruses.
摘要：
在2016年至2018年期间，巴西经历了严重的黄热病（YF）爆发，造成数百人伤亡。米纳斯吉拉斯州（MG）是受影响最大的州。这些爆发为评估野生型（WT）黄热病病毒（YFV）在人类中引发的免疫反应提供了独特的机会。斑块减少中和试验(PRNT)目前是通过测量中和抗体(nAbs)来评估对YFV的体液免疫应答的标准方法。本研究旨在通过使用带有WTYFV菌株的PRNTs来评估2017-2018年在不同疾病结局的MG中爆发的YF患者的体液免疫反应，与2017-2018年疫情隔离，和疫苗YFV株。对自然感染YF患者的样本进行了测试，与健康疫苗相比。结果表明，两组均呈现不同水平的抗WT和疫苗株的nAb，并且针对菌株的中和水平在同型和异型上变化。基于几何平均滴度（GMTs）的结果表明，YFV自然感染后的体液免疫反应可以达到比疫苗接种诱导的更高的水平（针对WTYFV的患者的GMT与疫苗接种者的GMT相比，P<0.0001)。这些发现表明由YFV的疫苗和WT株引发的体液免疫应答是不同的,可能是由于这些病毒之间的遗传和抗原差异。因此,目前评估自然感染YF个体免疫反应的方法和病毒循环密集地区的免疫监测方法可能需要更新.重要黄热病是由YFV引起的致命的高热疾病。尽管存在有效的疫苗，这种疾病仍然是全球公共卫生问题。关于针对YFV疫苗株的免疫反应，但是最近的研究表明，它与WT菌株诱导的不同。这种差异的程度及其背后的机制尚不清楚。因此，旨在更好地了解针对该病毒的免疫反应的研究是相关且必要的。本研究评估了巴西最近爆发的黄热病患者的中和抗体水平，与健康疫苗相比，使用WT和疫苗YFV株的斑块减少中和试验。结果表明，自然感染患者的体液免疫反应高于疫苗接种诱导的体液免疫反应，从而为针对这些病毒引发的免疫反应提供了新的见解。
