Influenza neuraminidase active site proximity assay for rapid profiling of inhibitory antibodies and antigenic drift.

IF 6.9 1区 医学 Q1 IMMUNOLOGY
Jin Gao, Galina Landgraf, Yue Yuan, Hai Yu, Soma Saeidi, Hyeog Kang, Mira Rakic Martinez, Luca Giurgea, Vladimir Lugovtsev, Jason Gorman, Matthew Memoli, Xi Chen, Zhiping Ye, Robert Daniels
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Abstract

Efficient approaches that can help to select vaccine strains for the influenza virus neuraminidase (NA) antigen are currently needed to advance the development of vaccines containing NA. Here, we present a rapid and cost-effective solution-based NA active site proximity assay (NASPA) for measuring NA activity inhibitory (NAI) antibodies. This simplified assay uses large "bulky" NA active site-binding inhibitors to replace the sialylated glycoprotein substrates in common NA enzyme-linked lectin assay (ELLA) approaches. Our results with ferret antisera and monoclonal antibodies against vaccine strain NAs show a strong correlation between NASPA and ELLA titers, and that NASPA titers are not influenced by anti-HA antibodies. Consequently, NASPA can be used with influenza A or B strains and with the latter it revealed incremental antigenic changes in the NAs from recent B Victoria lineage vaccine strains. By coupling NASPA with a simple activity assay, we also found that steric and active site-binding NAI antibodies against circulating NAs are common in adult human sera. Finally, we demonstrate that NASPA can be modified by incorporating novel NA substrate-analog-based inhibitors. Together, these results suggest that NASPA can aid the development of vaccines containing NA by helping to select suitable vaccine strains and profile anti-NA antibody responses.

流行性感冒神经氨酸酶活性位点接近测定快速分析抑制抗体和抗原漂移。
目前需要有效的方法来帮助选择流感病毒神经氨酸酶(NA)抗原的疫苗株,以推进含有NA的疫苗的开发。在这里,我们提出了一种快速且具有成本效益的基于溶液的NA活性位点接近试验(NASPA),用于测量NA活性抑制(NAI)抗体。这种简化的检测方法使用大的“笨重的”NA活性位点结合抑制剂来代替常见的NA酶联凝集素检测(ELLA)方法中的唾液化糖蛋白底物。我们对雪貂抗血清和针对NAs疫苗株的单克隆抗体的研究结果表明,NASPA滴度与ELLA滴度之间存在很强的相关性,并且NASPA滴度不受抗ha抗体的影响。因此,NASPA可用于甲型或乙型流感毒株,对乙型流感毒株,它揭示了最近的B维多利亚谱系疫苗毒株的NAs抗原的增量变化。通过将NASPA与简单的活性测定相结合,我们还发现针对循环NAs的立体和活性位点结合的NAI抗体在成人血清中很常见。最后,我们证明了NASPA可以通过加入新的NA底物-类似物抑制剂来修饰。总之,这些结果表明,NASPA可以通过帮助选择合适的疫苗株和描述抗NA抗体反应来帮助开发含有NA的疫苗。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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