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一场复杂的舞蹈:测量流感病毒进化与抗流感免疫反应的多维世界

A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses.

作者信息

Wang Jiong, Wiltse Alexander, Zand Martin S

机构信息

Department of Medicine, Division of Nephrology, University of Rochester Medical Center, Rochester, NY, 14534, USA.

Clinical and Translational Science Institute, University of Rochester Medical Center, Rochester, NY, 14534, USA.

出版信息

Pathogens. 2019 Nov 15;8(4):238. doi: 10.3390/pathogens8040238.

DOI:10.3390/pathogens8040238
PMID:31731815
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6963821/
Abstract

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to address this issue. However, the human antibody response is intricate and often obscure, with factors such as antigenic seniority or original antigenic sin (OAS), and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

摘要

人类对流感病毒感染或疫苗接种的抗体反应既复杂又对预防流感至关重要。病毒不断发生抗原变化以逃避人群免疫,这阻碍了每年疫苗株的选择,因为很难预测即将到来的流感季节会传播哪些病毒株。一种能够诱导广泛的跨流感亚型保护的“通用”流感疫苗将有助于解决这一问题。然而,人类抗体反应错综复杂且往往难以捉摸,存在抗原优先性或原始抗原罪(OAS)等因素,以及再次免疫增强,这确保了每个人对任何新的流感病毒株感染或疫苗接种都会产生独特的免疫反应。值得注意的是,重复接种疫苗后现有抗体对交叉保护免疫的影响尚不清楚。需要更多研究来确定其中的作用机制,但诸如血凝素抑制(HAI)和微量中和(MN)等传统检测方法在范围上过于有限,且资源消耗过大,无法有效应对这一挑战。在过去十年中,已经开发出了新的多维检测方法(MDA),通过以高通量方式用最少的样本同时测量针对大量流感血凝素(HA)蛋白的抗体,来帮助克服这些问题。MDA可能会成为加速流感疫苗接种体液免疫反应研究和通用流感疫苗开发的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b3/6963821/a5d39ff855ce/pathogens-08-00238-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b3/6963821/d7fa08c8e449/pathogens-08-00238-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b3/6963821/a5d39ff855ce/pathogens-08-00238-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b3/6963821/d7fa08c8e449/pathogens-08-00238-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b3/6963821/a5d39ff855ce/pathogens-08-00238-g002.jpg

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