Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype.
Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype.
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DOI：
10.1038/s41467-023-44330-8
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发表时间：
2024-01-09
影响因子：
16.6
通讯作者：
Harris, Eva
中科院分区：
文献类型：
--
作者：
Bos, Sandra;Graber, Aaron L.;Cardona-Ospina, Jaime A.;Duarte, Elias M.;Zambrana, Jose Victor;Ruiz Salinas, Jorge A.;Mercado-Hernandez, Reinaldo;Singh, Tulika;Katzelnick, Leah C.;de Silva, Aravinda;Kuan, Guillermina;Balmaseda, Angel;Harris, Eva
登革病毒（DENV1 - 4）是人类中最常见的虫媒病毒，是一个主要的公共卫生问题。了解调节登革病毒感染结果的免疫机制对疫苗研发至关重要。中和抗体（nAbs）是保护性免疫反应的一个重要组成部分，然而它们的检测往往依赖于单一的细胞底物和部分成熟的病毒粒子，这无法涵盖中和活性的全部范围，可能导致对中和抗体效力的有偏差的估计。在此，我们分析了在尼加拉瓜一项长期的儿童队列研究中，在一次或多次登革病毒感染之后，但在后续有症状或无症状的登革病毒1型、2型或3型感染之前收集的125个样本。通过使用有或无DC - SIGN的Vero细胞以及成熟或部分成熟的病毒粒子评估中和抗体反应，我们发现中和抗体效力和保护性的半数中和效价（NT50）临界值受细胞底物和病毒粒子成熟状态的极大影响。此外，中和抗体滴度与疾病预防之间的相关性取决于既往感染史和感染的血清型。最后，我们揭示了中和抗体组成的差异，这些差异在初次和二次既往感染后对预防有症状感染有不同的作用。这些发现对确定疫苗和自然感染的保护性抗体相关因素具有重要意义。
仍然需要提高对登革病毒特异性免疫的理解。在此，通过分析一个儿童队列中的抗体反应，作者表明中和抗体的保护能力取决于感染史和血清型，但其估计因检测条件和病毒粒子成熟程度而异。
Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections. There is still a need to improve understanding of dengue-specific immunity. Here, by analyzing the antibody response in a pediatric cohort the authors show that the protective capacity of neutralizing antibodies depends on infection history and serotype, but its estimation varies by assay condition and virion maturation.
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影响因子：
17.1
作者：
通讯作者：
--
DOI：
10.1016/s1473-3099(16)30473-x
发表时间：
2017-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Katzelnick LC;Coloma J;Harris E
通讯作者：
Harris E
影响因子：
2.7
作者：
Idris F;Muharram SH;Diah S
通讯作者：
Diah S
影响因子：
5.4
作者：
Boonnak, Kobporn;Slike, Bonnie M.;Marovich, Mary A.
通讯作者：
Marovich, Mary A.
影响因子：
6.4
作者：
Corbett, Kizzmekia S.;Katzelnick, Leah;de Silva, Aravinda M.
通讯作者：
de Silva, Aravinda M.