抗登革热IgG的聚焦化与疫苗接种后对登革热病毒感染的易感性增强有关

IF 14.6 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-09-24 DOI:10.1126/scitranslmed.adx7231

Usama Ashraf, Saborni Chakraborty, Courtney Scallan, Nathan C. Lo, Maria Theresa Alera, Aaron Farmer, Mary Noreen Cabalfin-Chua, Nelson L. Michael, Alan L. Rothman, Taia T. Wang

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引用次数: 0

摘要

登革热病毒（denv）每年导致3.9亿例感染，尽管这些感染中只有约25%有症状。虽然与严重DENV疾病相关的抗体特征已经得到了很好的研究，但影响感染易感性的因素仍然不太清楚。在这里，我们检测了DENV疫苗接种前后具有DENV暴露史的个体的免疫球蛋白G （IgG）特征，并将疫苗接种后感染的患者与未感染的患者进行比较。在疫苗接种前后出现的抗denv - a集中化升高与疫苗接种后感染的可能性增加有关。这些数据得到了机制研究的进一步支持，这些研究表明，非中和的、聚焦的、登卡夏后的IgG增强了小鼠的DENV复制。这种增强依赖于CD16，这是一个聚焦的IgG Fc结构域的受体。总之，这些发现支持一个模型，即集中的IgG的存在促进病毒复制，增加DENV暴露后产生性感染的可能性。此外，这些结果强调了IgG1聚焦化是DENV突破性感染风险的预测因子，并支持了研究疫苗接种过程中调节Fc聚焦化策略的重要性。

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Afucosylation of anti-dengue IgG is associated with enhanced susceptibility to dengue virus infection postvaccination

Dengue viruses (DENVs) cause 390 million infections annually, although only ~25% of these infections are symptomatic. Whereas antibody features linked to severe DENV disease are well studied, factors influencing infection susceptibility remain less clear. Here, we examined immunoglobulin G (IgG) characteristics before and after DENV vaccination (Dengvaxia) in individuals with a history of prior DENV exposure, comparing those who developed postvaccination infections to those who remained infection free. Elevated anti-DENV afucosylation, present before or after vaccination, was associated with increased likelihood of infection after vaccination. These data were further supported by mechanistic studies, which revealed that nonneutralizing, afucosylated, post-Dengvaxia IgG enhanced DENV replication in mice. This enhancement was dependent on CD16, the receptor for the afucosylated IgG Fc domain. Together, these findings support a model in which the presence of afucosylated IgG promotes virus replication, increasing the likelihood of productive infection upon DENV exposure. Moreover, these results highlight that IgG1 fucosylation is a predictor of risk for breakthrough DENV infection despite vaccination and support the importance of investigating strategies to regulate Fc fucosylation during vaccination.

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来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.