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Identification of Linear Peptide Immunogens with Verified Broad-spectrum Immunogenicity from the Conserved Regions within the Hemagglutinin Stem Domain of H1N1 Influenza Virus
Immunological Investigations ( IF 2.8 ) Pub Date : 2020-10-20 , DOI: 10.1080/08820139.2020.1834579
Shuang Li 1 , Yongbo Qiao 1 , Yan Xu 2 , Pengju Li 1 , Jiaojiao Nie 1 , Qi Zhao 3 , Wen Chai 4 , Yuhua Shi 1 , Wei Kong 1, 5 , Yaming Shan 1, 3, 5
Affiliation  

ABSTRACT

Background

Influenza A viruses (IAVs) induce acute respiratory disease and cause severe epidemics and pandemics. Since IAVs exhibit antigenic variation and genome reassortment, the development of broad-spectrum influenza vaccines is crucial. The stem of the hemagglutinin (HA) is highly conserved across IAV strains and thus has been explored in broad-spectrum influenza vaccine studies. The present study aimed to identify viral epitopes capable of eliciting effective host immune responses, which can be explored for the development of broad-spectrum non-strain specific prophylactic options against IAV.

Methods

In this study, a series of conserved linear sequences from the HA stem of IAV (H1N1) was recognized by sequence alignment and B/T-cell epitope prediction after being chemically coupled to the Keyhole Limpet Hemocyanin (KLH) protein. The predicted linear epitopes were identified by enzyme-linked immunosorbent assay (ELISA) after animal immunization and then fused with ferritin carriers.

Results

Three predicted linear epitopes with relatively strong immunogenicity, P3, P6 and P8 were fused with ferritin carriers P3F, P6F and P8F, respectively to further improve their immunogenicity. Antibody titre of the sera of mice immunized with the recombinant immunogens revealed the elicitation of specific antibody-binding activities by the identified sequences. While hemagglutinin-inhibition activities were not detected in the antisera, neutralizing antibodies against the H1 and H3 virus subtypes were detected by the microneutralization assay.

Conclusion

The linear epitopes fused with ferritin identified in this study can lay the foundation for future advancements in development of broad-spectrum subunit vaccine against IAV (H1N1), and give rise to the potential future applicability of ferritin-based antigen delivery nanoplatforms.



中文翻译:

从 H1N1 流感病毒血凝素干结构域内的保守区域鉴定具有验证的广谱免疫原性的线性肽免疫原

摘要

背景

甲型流感病毒 (IAV) 可诱发急性呼吸道疾病并引起严重的流行病和大流行。由于 IAV 表现出抗原变异和基因组重排,因此开发广谱流感疫苗至关重要。血凝素 (HA) 的茎在 IAV 毒株中高度保守,因此已在广谱流感疫苗研究中进行了探索。本研究旨在鉴定能够引发有效宿主免疫反应的病毒表位,可用于开发针对 IAV 的广谱非菌株特异性预防选择。

方法

在这项研究中,IAV (H1N1) 的 HA 茎中的一系列保守线性序列在与 Keyhole Limpet Hemocyanin (KLH) 蛋白化学偶联后被序列比对和 B/T 细胞表位预测识别。动物免疫后通过酶联免疫吸附试验(ELISA)鉴定预测的线性表位,然后与铁蛋白载体融合。

结果

三个具有较强免疫原性的预测线性表位P3、P6和P8分别与铁蛋白载体P3F、P6F和P8F融合以进一步提高它们的免疫原性。用重组免疫原免疫的小鼠血清的抗体滴度揭示了鉴定的序列引发了特异性抗体结合活性。虽然在抗血清中未检测到血凝素抑制活性,但通过微量中和试验检测到针对 H1 和 H3 病毒亚型的中和抗体。

结论

本研究中鉴定的与铁蛋白融合的线性表位可为未来开发抗 IAV (H1N1) 广谱亚单位疫苗奠定基础,并为未来基于铁蛋白的抗原递送纳米平台的潜在应用提供支持。

更新日期:2020-10-20
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