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抗原表位免疫优势重定向后重复变异暴露。

Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure.

机构信息

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.

出版信息

Viruses. 2022 Jun 14;14(6):1293. doi: 10.3390/v14061293.

DOI:10.3390/v14061293
PMID:35746763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9229260/
Abstract

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes.

摘要

人类诺如病毒是急性肠胃炎的主要病因，其抗原变体由 GII.4 基因型驱动。成年人对 GII.4 疫苗的抗体反应受免疫记忆的影响。尚未有报道表明没有广泛免疫记忆的儿童对 GII.4 疫苗的反应如何。在这里，我们使用替代测定法和抗原位点嵌合病毒样颗粒来描述 GII.4 中和抗体（nAb）的自然感染后景观。我们证明 nAb 景观随年龄和病毒暴露而变化。在 A、C 和 G 位点中，首次感染的 nAb 主要集中在 A 和 C 位点。随着年龄/暴露而产生的免疫力增强，A 位点补充了可以连接 A 位点到 C 和 G 位点的抗体。跨位点 nAb 持续发育到成年期，同时对 G 位点的 nAb 增加。持续接触 GII.4 2012 年悉尼变体与 A 和 G 位点的共同主导地位相关。此外，G 位点 nAb 与针对抗原差异变体的 nAb 滴度变宽相关。这些数据描述了一生中对 GII.4 免疫的发展的基本步骤，并说明了一种大流行变体的抗原性如何通过免疫显性表位的重新定向来影响另一种变体的大流行潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/ddd3c63be931/viruses-14-01293-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/b18367d2cb55/viruses-14-01293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/1abf7334fe0c/viruses-14-01293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/7a585a7dfa34/viruses-14-01293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/f7bdae3a4e73/viruses-14-01293-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/13a615094ae9/viruses-14-01293-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/ddd3c63be931/viruses-14-01293-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/b18367d2cb55/viruses-14-01293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/1abf7334fe0c/viruses-14-01293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/7a585a7dfa34/viruses-14-01293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/f7bdae3a4e73/viruses-14-01293-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/13a615094ae9/viruses-14-01293-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b1/9229260/ddd3c63be931/viruses-14-01293-g006.jpg

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