Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, United States.
Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT, United States.
Front Immunol. 2023 Aug 18;14:1229724. doi: 10.3389/fimmu.2023.1229724. eCollection 2023.
Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb-infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection.
基因群 II（GII）诺如病毒是高收入和低收入国家儿童腹泻疾病负担的主要原因。GII.17 诺如病毒由不同的遗传簇（I、II、IIIa 和 IIIb）组成，并且有取代历史上更为流行的 GII.4 株的潜力，但 GII.17 抗原多样性的血清学基础尚未在儿童中进行研究。利用来自出生队列的样本，我们研究了确认的 GII.17 感染幼儿中 GII.17 簇变体的抗体和 B 细胞反应，并证明了不同的遗传簇共同循环。多克隆血清抗体结合多个簇，但在替代病毒中和测定中显示簇特异性阻断活性。来自婴儿 GII.17 病例的永生记忆 B 细胞（MBC）分泌的抗体高度特异于 GII.17，并对该基因型表现出阻断活性。我们分离了一种 MBC 衍生的 GII.17 特异性免疫球蛋白 A（IgA）单克隆抗体，称为 NVA.1，它能有效且特异性地阻断 GII.17 簇 IIIb，并识别针对感染簇 IIIb 儿童血清的表位。这些数据表明，多种抗原上不同的 GII.17 变体在幼儿中共同循环，表明在感染期间存在抗体定义的簇特异性表位的情况下，保留了簇多样性和潜在的免疫逃逸能力。
