Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection.
Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection.
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DOI：
10.1126/scitranslmed.abm3151
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发表时间：
2022-06-29
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
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作者：
预先存在的交叉反应抗体在后续感染不同登革热病毒（DENV）血清型（DENV1 - 4）期间与保护作用和发病机制均有关联。然而，体液免疫相关因素和保护机制仍然难以捉摸。我们使用系统血清学方法评估体液反应，对从尼加拉瓜的儿童队列中在无症状或有症状的二次登革热病毒3型（DENV3）感染前收集的血浆进行了分析。免受有症状感染的儿童比有症状的儿童具有更多的抗包膜（E）和抗非结构蛋白1（NS1）总IgG、IgG4以及更强的Fc效应功能。Fc效应功能还与无症状前组免受出血表现相关。此外，使用这些血浆样本进行的体外病毒学检测显示，抗体依赖性补体沉积介导的保护作用与病毒粒子的裂解以及登革热病毒感染细胞相关。这些数据表明，E和NS1特异性Fc功能可能作为保护作用的相关因素，这可能潜在地应用于登革热疫苗的设计和评估。
抗体Fc特性和效应功能与免受有症状的登革热病毒3型感染相关。
Pre-existing cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1–4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort in Nicaragua. Children protected from symptomatic infections had more anti-envelope (E) and anti-nonstructural protein 1 (NS1) total IgG, IgG4, and greater Fc effector functions than those with symptoms. Fc effector functions were also associated with protection from hemorrhagic manifestations in the pre-symptomatic group. Furthermore, in vitro virological assays using these plasma samples revealed that protection mediated by antibody-dependent complement deposition was associated with both lysis of virions and DENV-infected cells. These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines. Antibody Fc characteristics and effector functions correlate with protection from symptomatic DENV3 infection.
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影响因子：
15.8
作者：
Huber, Michael;Fischer, Marek;Misselwitz, Benjamin;Manrique, Amapola;Kuster, Herbert;Niederoest, Barbara;Weber, Rainer;von Wyl, Viktor;Guenthard, Huldrych F.;Trkola, Alexandra
通讯作者：
Trkola, Alexandra
影响因子：
7.3
作者：
Collins AM;Jackson KJ
通讯作者：
Jackson KJ
影响因子：
4
作者：
Jackson, Katherine J. L.;Wang, Yan;Collins, Andrew M.
通讯作者：
Collins, Andrew M.
DOI：
10.1126/science.abc7303
发表时间：
2021-06-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bournazos S;Vo HTM;Duong V;Auerswald H;Ly S;Sakuntabhai A;Dussart P;Cantaert T;Ravetch JV
通讯作者：
Ravetch JV
影响因子：
64.5
作者：
Chung AW;Kumar MP;Arnold KB;Yu WH;Schoen MK;Dunphy LJ;Suscovich TJ;Frahm N;Linde C;Mahan AE;Hoffner M;Streeck H;Ackerman ME;McElrath MJ;Schuitemaker H;Pau MG;Baden LR;Kim JH;Michael NL;Barouch DH;Lauffenburger DA;Alter G
通讯作者：
Alter G